Professor Derek Laver

Professor Derek Laver

Professor

School of Biomedical Sciences and Pharmacy (Human Physiology)

Career Summary

Biography

My research brings together physics, engineering and biology to understand the complex molecular and electrochemical mechanisms controlling heart contraction and rhythm. This entails sophisticated experimental techniques in which single molecules are embedded into artificial membranes where the effects of natural biochemicals or drugs can be measured and then analysed using computation modelling.  My research group is advancing our understanding of the function and role of ion channels that control muscle contraction and the heart rhythm. Contraction occurs in response to the release of calcium from the sarcoplasmic reticulum (SR, the intracellular calcium store). Calcium is released via SR calcium release channels known as ryanodine receptors (RyR), which are not only responsible for contractile force, but also heart rhythm. Our computational physiology has produced the first feasible solution to the old problem of how calcium release from the SR, once initiated, can be terminated, an explanation now accepted by the field. Our experiments have produced insight into how mutations in RyRs or their associated proteins lead to human disorders such as malignant hyperthermia in skeletal muscle and sudden death cardiac arrhythmias. We have recently discovered the mechanism of action of two, clinically significant, anti-arrhythmic drugs; flecainide and dantrolene, which paves the way for understanding how anti-arrhythmic drugs work.

My research group is comprised of Mr Paul Johnson (research assistant), Dr Kafa Walweel (Post Doctoral Fellow) and Mr Yury Nikoleav, Mr Amir Ashna and Ms Sonia Tamanna (PhD students). Together we are addressing the following questions:

How do calcium release channels (RyRs) regulate heart contraction and rhythm?We are answering this question in collaboration with Professor Mark Cannell at Bristol University. Our approach is to develop computational models to provide a way to integrate Ca2+/Mg2+ regulation of RyRs with heart function at the level of the cell, tissue and whole organ. In our hands, these models proved highly effective because they could cope with complex organelle architecture and cellular biochemical and electrical interactions that defy intuitive interpretation. We developed the first 3D computer model of cardiac calcium release which identified the first plausible negative-regulation mechanism for SR Ca2+ release that counters the inherently regenerative process of calcium induced calcium release, this providing an explanation for the longstanding (25-years) problem of how Ca2+ release is controlled during heart contraction.

How does dysregulation of RyRs lead to cardiac arrhythmias?With Professor Bjorn Knollmann (Vanderbilt University) we found that pro-arrhythmic agents such as tricyclic antidepressants increased RyR activity (Chopra et al., 2009) demonstrating that RyR dysregulation by gain of function underlies several types of cardiac arrhythmia. We are now we are studying the mechanisms of an inherited adrenergic stress-induced arrhythmia called catecholaminergic polymorphic ventricular tachycardia (CPVT).  CPVT is caused by excessive calcium release due to mutations in genes that control cardiac SR Ca2+ release, i.e. the RyR and its complex with the SR Ca2+ buffering protein calsequestrin. CPVT has a 35% mortality rate in individuals under 30 with Sudden Cardiac Death frequently being the first symptom. We were the first to show that calmodulin mutations also lead to a RyR gain of function during adrenergic stimulation. (Hwang et al., 2014, Walweel et al 2017).

How may pharmacological interventions targeting RyRs restore normal heart rhythm?In collaboration with Knollmann’s group, we began investigations of the efficacy of anti-arrhythmic agents in treatment of CPVT. One drug tested was flecainide, a sarcolemmal Na+ channel blocker used for treatment of atrial arrhythmias. Serendipitously, we found that flecainide completely prevented CPVT in 86% of 35 patients with calsequestrin and RyR mutations, patients that were unresponsive to standard drug treatments. Most significantly, we discovered that suppression of CPVT induced arrhythmias by flecainide is due to its combined suppression of 1) spontaneous SR Ca2+ release events by RyR inhibition, and 2) triggered beats by Na+ channel block. This action of flecainide on RyRs uncovered an entirely new mechanism by which arrhythmias can be prevented and showed for the first time that RyRs can indeed be a therapeutic target for anti-arrhythmic drugs (Watanabe et al., 2009) Our most recent publication in the journal, Molecular Pharmacology, reports another novel mechanism of action for anti-arrhythmic drugs. We show for the first time that the association of calmodulin with the RyR is essential for the action of muscle relaxing/anti-arrhythmic drugs such as dantrolene (Oo et al., 2015). This work has provided a major leap forward in our understanding of the mechanism of action of a drug that has been in clinical use for over 50 years.


Qualifications

  • PhD, University of New South Wales
  • Bachelor of Science (Honours)(Physics), University of New South Wales

Keywords

  • Ion channels
  • Membrane transport
  • cardiac muscle
  • disease
  • electrophysiology
  • ryanodine receptors
  • skeletal muscle

Fields of Research

Code Description Percentage
029999 Physical Sciences not elsewhere classified 20
111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified 60
111699 Medical Physiology not elsewhere classified 20

Professional Experience

UON Appointment

Title Organisation / Department
Professor University of Newcastle
School of Biomedical Sciences and Pharmacy
Australia

Academic appointment

Dates Title Organisation / Department
1/01/2002 - 31/12/2007 UoN - Gladys M Brawn Senior Research Fellowship The University of Newcastle
Australia
1/01/2001 - 1/12/2005 Professorial Research Fellow (ARC) University of Newcastle
Health
Australia
1/01/1999 - 1/12/2000 Senior Research Officer (National Health & Medical Research Council) Australian National University
Biochemistry and Molecular Biology
Australia
1/01/1997 - 1/12/1998 Senior Research Officer Australian National University
John Curtin School of Medical Research
Australia
1/01/1992 - 1/12/2005 Prestigious fellowship Senior Research Fellow (ARC)
Australia

Teaching appointment

Dates Title Organisation / Department
1/01/2010 - 31/12/2016 Associate Professor The University of Newcastle
Australia

Invitations

External Reviewer - Programs

Year Title / Rationale
2004 Biomembrane program,
Organisation: AgResearch

Participant

Year Title / Rationale
2006 Gordon Conference on Muscle
Organisation: Gordon conferences Description: Platform presentation at a Gordon conference is restricted to high profile scientists with high impact work
2003 Gordon conference on excitation contraction coupling
Organisation: Gordon conference Description: Platform presentation at a Gordon conference is restricted to high profile scientists with high impact work
2001 IUPS satelite confernece
Organisation: IUPS

Speaker

Year Title / Rationale
2017 International Society for Heart Research
2016 International Society for Heart Research
2016 Gage conference on muscle
2015 Australia Pacific Heart Rhythm Society
2015 International Society for Heart Research
2014 World Congress of Cardiology
2014 Union of Pure and Applied Biophysics
2013 International Society for Heart Research
2012 Gordon Conference on E-C coupling
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Book (1 outputs)

Year Citation Altmetrics Link
2002 Dulhunty AR, Laver DR, A Ca2+-activated anion channel in the sarcoplasmic reticulum of skeletal muscle, ACADEMIC PRESS INC, 22 (2002)
DOI 10.1016/S1063-5823(02)53028-3

Chapter (2 outputs)

Year Citation Altmetrics Link
2010 Laver DR, 'Regulation of RyR Channel Gating by Ca2+, Mg2+ and ATP', Structure and Function of Calcium Release Channels, Academic Press, Waltham 69-89 (2010) [B1]
Citations Scopus - 8Web of Science - 7
2009 Laver DR, 'Electrical methods for determining surface charge density and electrolyte composition at the lipid bilayer-solution interface', Advances in Planar Lipid Bilayers and Liposomes, Elsevier, Amsterdam 87-105 (2009) [B1]
DOI 10.1016/S1554-4516(09)09004-8

Journal article (97 outputs)

Year Citation Altmetrics Link
2017 Walweel K, Oo YW, Laver DR, 'The emerging role of calmodulin regulation of RyR2 in controlling heart rhythm, the progression of heart failure and the antiarrhythmic action of dantrolene', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 44 135-142 (2017)
DOI 10.1111/1440-1681.12669
Citations Web of Science - 1
2017 van Helden DF, Kamiya A, Kelsey S, Laver DR, Jobling P, Mitsui R, Hashitani H, 'Nerve-induced responses of mouse vaginal smooth muscle.', Pflugers Arch, (2017)
DOI 10.1007/s00424-017-1995-x
Co-authors Phillip Jobling, Dirk Vanhelden
2017 Walweel K, Gomez-Hurtado N, Oo YW, Beard NA, Dos Remedios C, Johnson CN, et al., 'Calmodulin Mutants Linked to Catecholaminergic Polymorphic Ventricular Tachycardia Fail to Inhibit Human RyR2 Channels.', J Am Coll Cardiol, 70 115-117 (2017)
DOI 10.1016/j.jacc.2017.04.055
2017 Laver DR, Attia J, Oldmeadow C, Quail AW, 'Cardiac Calcium Release Channel (Ryanodine Receptor 2) Regulation by Halogenated Anesthetics.', Anesthesiology, 126 495-506 (2017)
DOI 10.1097/ALN.0000000000001519
Citations Scopus - 1Web of Science - 1
Co-authors Christopher Oldmeadow, Tony Quail, John Attia
2017 Walweel K, Molenaar P, Imtiaz MS, Denniss A, Dos Remedios C, van Helden DF, et al., 'Ryanodine receptor modification and regulation by intracellular Ca(2+) and Mg(2+) in healthy and failing human hearts.', J Mol Cell Cardiol, 104 53-62 (2017)
DOI 10.1016/j.yjmcc.2017.01.016
Citations Scopus - 1Web of Science - 1
Co-authors Dirk Vanhelden
2016 Laver DR, 'Balancing SR Ca2+ uptake and release in the cycle of heart rhythm', JOURNAL OF PHYSIOLOGY-LONDON, 594 2779-2780 (2016)
DOI 10.1113/JP272063
2015 Zhang HM, Imtiaz MS, Laver DR, McCurdy DW, Offler CE, Van Helden DF, Patrick JW, 'Polarized and persistent Ca2+ plumes define loci for formation of wall ingrowth papillae in transfer cells', Journal of Experimental Botany, 66 1179-1190 (2015) [C1]

© The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. Transfer cell morphology is characterized by a polarized ingrowth wall ... [more]

© The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. Transfer cell morphology is characterized by a polarized ingrowth wall comprising a uniform wall upon which wall ingrowth papillae develop at right angles into the cytoplasm. The hypothesis that positional information directing construction of wall ingrowth papillae is mediated by Ca 2+ signals generated by spatiotemporal alterations in cytosolic Ca 2+ ([Ca 2+ ] cyt ) of cells trans-differentiating to a transfer cell morphology was tested. This hypothesis was examined using Vicia faba cotyledons. On transferring cotyledons to culture, their adaxial epidermal cells synchronously trans-differentiate to epidermal transfer cells. A polarized and persistent Ca 2+ signal, generated during epidermal cell trans-differentiation, was found to co-localize with the site of ingrowth wall formation. Dampening Ca 2+ signal intensity, by withdrawing extracellular Ca 2+ or blocking Ca 2+ channel activity, inhibited formation of wall ingrowth papillae. Maintenance of Ca 2+ signal polarity and persistence depended upon a rapid turnover (minutes) of cytosolic Ca 2+ by co-operative functioning of plasma membrane Ca 2+ -permeable channels and Ca 2+ -ATPases. Viewed paradermally, and proximal to the cytosol-plasma membrane interface, the Ca 2+ signal was organized into discrete patches that aligned spatially with clusters of Ca 2+ -permeable channels. Mathematical modelling demonstrated that these patches of cytosolic Ca 2+ were consistent with inward-directed plumes of elevated [Ca 2+ ] cyt . Plume formation depended upon an alternating distribution of Ca 2+ -permeable channels and Ca 2+ -ATPase clusters. On further inward diffusion, the Ca 2+ plumes coalesced into a uniform Ca 2+ signal. Blocking or dispersing the Ca 2+ plumes inhibited deposition of wall ingrowth papillae, while uniform wall formation remained unaltered. A working model envisages that cytosolic Ca 2+ plumes define the loci at which wall ingrowth papillae are deposited.

DOI 10.1093/jxb/eru460
Citations Scopus - 6Web of Science - 7
Co-authors David Mccurdy, John Patrick, Tina Offler, Dirk Vanhelden
2015 Nikolaev YA, Dosen PJ, Laver DR, Van Helden DF, Hamill OP, 'Single mechanically-gated cation channel currents can trigger action potentials in neocortical and hippocampal pyramidal neurons', Brain Research, 1608 1-13 (2015) [C1]

© 2015 Elsevier B.V. All rights reserved. The mammalian brain is a mechanosensitive organ that responds to different mechanical forces ranging from intrinsic forces implicated in... [more]

© 2015 Elsevier B.V. All rights reserved. The mammalian brain is a mechanosensitive organ that responds to different mechanical forces ranging from intrinsic forces implicated in brain morphogenesis to extrinsic forces that can cause concussion and traumatic brain injury. However, little is known of the mechanosensors that transduce these forces. In this study we use cell-attached patch recording to measure single mechanically-gated (MG) channel currents and their affects on spike activity in identified neurons in neonatal mouse brain slices. We demonstrate that both neocortical and hippocampal pyramidal neurons express stretch-activated MG cation channels that are activated by suctions of ~25 mm Hg, have a single channel conductance for inward current of 50-70 pS and show weak selectivity for alkali metal cations (i.e., Na < sup > + < /sup > < K < sup > + < /sup > < Cs < sup > + < /sup > ). Significantly, single MG channel currents activated on the soma trigger spiking/action potentials in bot h neocortical and hippocampal pyramidal neurons. Not all neuron types studied here expressed MG channel currents. In particular, locus coeruleus and cerebellar Purkinje neurons showed no detectable MG channel activity. Moreover their robust rhythmic spike activity was resistant to mechanical modulation. Our observation that a single MG channel current can trigger spiking predicates the need for reassessment of the long held view that the impulse output of central neurons depends only upon their intrinsic voltage-gated channels and/or their integrated synaptic input.

DOI 10.1016/j.brainres.2015.02.051
Co-authors Dirk Vanhelden
2015 Walweel K, Laver DR, 'Mechanisms of SR calcium release in healthy and failing human hearts.', Biophys Rev, 7 33-41 (2015)
DOI 10.1007/s12551-014-0152-4
2015 Oo YW, Gomez-Hurtado N, Walweel K, van Helden DF, Imtiaz MS, Knollmann BC, Laver DR, 'Essential Role of Calmodulin in RyR Inhibition by Dantrolene', MOLECULAR PHARMACOLOGY, 88 57-63 (2015) [C1]
DOI 10.1124/mol.115.097691
Citations Scopus - 15Web of Science - 12
Co-authors Dirk Vanhelden
2015 Walweel K, Laver DR, 'Mechanisms of SR calcium release in healthy and failing human hearts', Biophysical Reviews, 7 33-41 (2015) [C1]
DOI 10.1007/s12551-014-0152-4
2014 van Helden DF, Thomas PA, Dosen PJ, Imtiaz MS, Laver DR, Isbister GK, 'Pharmacological approaches that slow lymphatic flow as a snakebite first aid.', PLoS Negl Trop Dis, 8 e2722 (2014) [C1]
DOI 10.1371/journal.pntd.0002722
Citations Scopus - 5Web of Science - 5
Co-authors Geoffrey Isbister, Dirk Vanhelden
2014 Walweel K, Li J, Molenaar P, Imtiaz MS, Quail A, dos Remedios CG, et al., 'Differences in the regulation of RyR2 from human, sheep, and rat by Ca²¿ and Mg²¿ in the cytoplasm and in the lumen of the sarcoplasmic reticulum.', J Gen Physiol, 144 263-271 (2014) [C1]
DOI 10.1085/jgp.201311157
Citations Scopus - 6Web of Science - 6
Co-authors Dirk Vanhelden, Tony Quail
2014 Hwang HS, Nitu FR, Yang Y, Walweel K, Pereira L, Johnson CN, et al., 'Divergent Regulation of Ryanodine Receptor 2 Calcium Release Channels by Arrhythmogenic Human Calmodulin Missense Mutants', CIRCULATION RESEARCH, 114 1114-1124 (2014) [C1]
DOI 10.1161/CIRCRESAHA.114.303391
Citations Scopus - 40Web of Science - 37
2014 Mehra D, Imtiaz MS, Van Helden DF, Knollmann BC, Laver DR, 'Multiple modes of ryanodine receptor 2 inhibition by flecainide', Molecular Pharmacology, 86 696-706 (2014) [C1]

Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics. Catecholaminergic polymorphic ventricular tachycardia (CPVT) causes sudden cardiac death ... [more]

Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics. Catecholaminergic polymorphic ventricular tachycardia (CPVT) causes sudden cardiac death due to mutations in cardiac ryanodine receptors (RyR2), calsequestrin, or calmodulin. Flecainide, a class I antiarrhythmic drug, inhibits Na < sup > + < /sup > and RyR2 channels and prevents CPVT. The purpose of this study is to identify inhibitory mechanisms of flecainide on RyR2. RyR2 were isolated from sheep heart, incorporated into lipid bilayers, and investigated by singlechannel recording under various activating conditions, including the presence of cytoplasmic ATP (2mM) and a range of cytoplasmic [Ca < sup > 2+ < /sup > ], [Mg < sup > 2+ < /sup > ], pH, and [caffeine] . Flecainide applied to either the cytoplasmic or luminal sides of the membrane inhibited RyR2 by two distinct modes: 1) a fast block consisting of brief substate and closed events with a mean duration of ~1 ms, and 2) a slow block consisting of closed events with a mean duration of ~1 second. Both inhibition modes were alleviated by increasing cytoplasmic pH from 7.4 to 9.5 but were unaffected by luminal pH. The slow block was potentiated in RyR2 channels that had relatively low open probability, whereas the fast block was unaffected by RyR2 activation. These results show that these two modes are independent mechanisms for RyR2 inhibition, both having a cytoplasmic site of action. The slow mode is a closed-channel block, whereas the fast mode blocks RyR2 in the open state. At diastolic cytoplasmic [Ca < sup > 2+ < /sup > ] (100 nM), flecainide possesses an additional inhibitory mechanism that reduces RyR2 burst duration. Hence, multiple modes of action underlie RyR2 inhibition by flecainide.

DOI 10.1124/mol.114.094623
Citations Scopus - 8Web of Science - 8
Co-authors Dirk Vanhelden
2013 Li J, Imtiaz MS, Beard NA, Dulhunty AF, Thorne R, vanHelden DF, Laver DR, 'ß-Adrenergic stimulation increases RyR2 activity via intracellular Ca2+ and Mg2+ regulation.', PLoS One, 8 e58334 (2013) [C1]
DOI 10.1371/journal.pone.0058334
Co-authors Rick Thorne, Dirk Vanhelden
2013 Cannell MB, Kong CHT, Imtiaz MS, Laver DR, 'Control of Sarcoplasmic Reticulum Ca2+ Release by Stochastic RyR Gating within a 3D Model of the Cardiac Dyad and Importance of Induction Decay for CICR Termination', BIOPHYSICAL JOURNAL, 104 2149-2159 (2013) [C1]
DOI 10.1016/j.bpj.2013.03.058
Citations Scopus - 35Web of Science - 35
2013 Laver DR, Kong CHT, Imtiaz MS, Cannell MB, 'Termination of calcium-induced calcium release by induction decay: An emergent property of stochastic channel gating and molecular scale architecture', JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 54 98-100 (2013) [C1]
DOI 10.1016/j.yjmcc.2012.10.009
Citations Scopus - 30Web of Science - 26
2013 Kong CHT, Laver DR, Cannell MB, 'Extraction of Sub-microscopic Ca Fluxes from Blurred and Noisy Fluorescent Indicator Images with a Detailed Model Fitting Approach', PLOS COMPUTATIONAL BIOLOGY, 9 (2013) [C1]
DOI 10.1371/journal.pcbi.1002931
Citations Scopus - 11Web of Science - 9
2012 Seymour VAL, Curmi JP, Howitt SM, Casarotto MG, Laver DR, Tierney ML, 'Selective modulation of different GABA A receptor isoforms by diazepam and etomidate in hippocampal neurons', International Journal of Biochemistry and Cell Biology, 44 1491-1500 (2012) [C1]
Citations Scopus - 4Web of Science - 4
2011 Hwang HS, Hasdemir C, Laver DR, Mehra DR, Turhan K, Faggioni M, et al., 'Inhibition of Cardiac Ca2+ Release Channels (RyR2) Determines Efficacy of Class I Antiarrhythmic Drugs in Catecholaminergic Polymorphic Ventricular Tachycardia', Circulation: Arrhythmia and Electrophysiology, 4 128-135 (2011) [C1]
Citations Scopus - 76Web of Science - 56
2011 Laver DR, Van Helden DF, 'Three independent mechanisms contribute to tetracaine inhibition of cardiac calcium release channels', Journal of Molecular and Cellular Cardiology, 51 357-369 (2011) [C1]
DOI 10.1016/j.yjmcc.2011.05.009
Citations Scopus - 9Web of Science - 10
Co-authors Dirk Vanhelden
2010 Hwang HS, Hasdemir C, Laver D, Mehra D, Turhan K, Faggioni M, et al., 'Inhibition of Cardiac Ca2+ Release Channels (RyR2) Determines Efficacy of Class I Antiarrhythmic Drugs in Catecholaminergic Polymorphic Ventricular Tachycardia', CIRCULATION, 122 (2010) [C3]
2010 Imtiaz MS, Von Der Weid P-Y, Laver DR, Van Helden DF, 'SR Ca2+ store refill-a key factor in cardiac pacemaking', Journal of Molecular and Cellular Cardiology, 49 412-426 (2010) [C1]
DOI 10.1016/j.yjmcc.2010.03.015
Citations Scopus - 9Web of Science - 7
Co-authors Dirk Vanhelden
2010 Hilliard FA, Steele DS, Laver DR, Yang Z, Le Marchand SJ, Chopra N, et al., 'Flecainide inhibits arrhythmogenic Ca2+ waves by open state block of ryanodine receptor Ca2+ release channels and reduction of Ca2+ spark mass', Journal of Molecular and Cellular Cardiology, 48 293-301 (2010) [C1]
DOI 10.1016/j.yjmcc.2009.10.005
Citations Scopus - 137Web of Science - 113
2010 Shtifman A, Ward CW, Laver DR, Bannister ML, Lopez JR, Kitazawa M, et al., 'Amyloid-ß protein impairs Ca2+ release and contractility in skeletal muscle', Neurobiology of Aging, 31 2080-2090 (2010) [C1]
DOI 10.1016/j.neurobiolaging.2008.11.003
Citations Scopus - 27Web of Science - 24
2010 Van Helden DF, Laver DR, Holdsworth JL, Imtiaz MS, 'Generation and propagation of gastric slow waves', Clinical and Experimental Pharmacology and Physiology, 37 516-524 (2010) [C1]
DOI 10.1111/j.1440-1681.2009.05331.x
Citations Scopus - 33Web of Science - 29
Co-authors John Holdsworth, Dirk Vanhelden
2009 Laver D, 'Chapter 4 Electrical Methods for Determining Surface Charge Density and Electrolyte Composition at the Lipid Bilayer-Solution Interface', Advances in Planar Lipid Bilayers and Liposomes, 9 87-105 (2009)

In this chapter I will review electrical methods for inferring the surface potential and surface charge density on lipid bilayers and the electrolyte composition at the bilayer in... [more]

In this chapter I will review electrical methods for inferring the surface potential and surface charge density on lipid bilayers and the electrolyte composition at the bilayer interface. I will review the early studies which measured electrostatic potentials between the bilayer interior and the external solution. These include methods based on ionophores, open circuit potential measurements, the inner field compensation and measurements of the ionic double-layer capacitance. I will then go on to review two methods which I developed for inferring changes in solute concentrations (solution transients) at a bilayer surface during solution changes which also allows simultaneous measurement of single channel activity. These methods (1) use fast solution changes with induce a shift in bilayer potential that can generate a transient, capacitive current through the bilayer under voltage-clamp conditions and (2) use ion channels embedded in the bilayer to sense solute concentrations during solution exchange. © 2009 Elsevier Inc. All rights reserved.

DOI 10.1016/S1554-4516(09)09004-8
Citations Scopus - 1
2009 Chopra N, Laver DR, Davies SS, Knollmann BC, 'Amitriptyline activates cardiac ryanodine channels and causes spontaneous sarcoplasmic reticulum calcium release', Molecular Pharmacology, 75 183-195 (2009) [C1]
DOI 10.1124/mol.108.051490
Citations Scopus - 17Web of Science - 16
2009 Laver DR, 'Luminal Ca2+ activation of cardiac ryanodine receptors by luminal and cytoplasmic domains', European Biophysics Journal, 39 19-26 (2009) [C1]
DOI 10.1007/s00249-009-0417-1
Citations Scopus - 20Web of Science - 18
2009 Everitt AB, Seymour VAL, Curmi J, Laver DR, Gage PW, Tierney ML, 'Protein interactions involving the gamma 2 large cytoplasmic loop of GABA(A) receptors modulate conductance', FASEB Journal, 23 4361-4369 (2009) [C1]
DOI 10.1096/fj.09-137042
Citations Scopus - 12Web of Science - 12
2009 Watanabe H, Chopra N, Laver DR, Hwang HS, Davies SS, Roach DE, et al., 'Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans', Nature Medicine, 15 380-383 (2009) [C1]
DOI 10.1038/nm.1942
Citations Scopus - 330Web of Science - 262
2008 Laver DR, Honen BN, 'Luminal Mg2+, a key factor controlling RYR2-mediated Ca2+ release: Cytoplasmic and luminal regulation modeled in a tetrameric channel', Journal of General Physiology, 132 429-446 (2008) [C1]
DOI 10.1085/jgp.200810001
Citations Scopus - 35Web of Science - 31
2008 Laver DR, Honen BN, Lamb GD, Ikemoto N, 'A domain peptide of the cardiac ryanodine receptor regulates channel sensitivity to luminal Ca2+ via cytoplasmic Ca2+ sites', European Biophysics Journal with Biophysics Letters, 37 455-467 (2008) [C1]
DOI 10.1007/s00249-007-0238-z
Citations Scopus - 9Web of Science - 9
2007 Laver DR, 'Ca2+ stores regulate ryanodine receptor Ca2+ release channels via luminal and cytosolic Ca2+ sites', Clinical and Experimental Pharmacology and Physiology, 34 889-896 (2007) [C1]
DOI 10.1111/j.1440-1681.2007.04708.x
Citations Scopus - 41Web of Science - 42
2007 Laver DR, 'Ca2+ stores regulate ryanodine receptor Ca2+ release channels via luminal and cytosolic Ca2+ sites', Biophysical Journal, 92 3541-3555 (2007) [C1]
DOI 10.1529/biophysj.106.099028
Citations Scopus - 69Web of Science - 71
2007 Laver DR, Hamada T, Fessenden JD, Ikemoto N, 'The ryanodine receptor pore blocker neomycin also inhibits channel activity via a previously undescribed high-affinity Ca2+ binding site', Journal of Membrane Biology, 220 11-20 (2007) [C1]
DOI 10.1007/s00232-007-9067-3
Citations Scopus - 5Web of Science - 5
2006 Laver DR, 'Regulation of ryanodine receptors from skeletal and cardiac muscle during rest and excitation', Clinical and Experimental Pharmacology & Physiology, 33 1107-1113 (2006) [C1]
DOI 10.1111/j.1440-1681.2006.04500.x
Citations Scopus - 12Web of Science - 12
2006 Laver DR, Bradley KM, 'Disulfonic stilbene permeation and block of the anion channel from the sarcoplasmic reticulum of rabbit skeletal muscle', American Journal of Physiology-Cell Physiology, 290 C1666-C1677 (2006) [C1]
DOI 10.1152/ajpcell.00299.2005
Citations Scopus - 9Web of Science - 8
2006 Lindquist CEL, Laver DR, Birnir B, 'The mechanism of SR95531 inhibition at GABA(A) receptors examined in human alpha(1)beta(1) and alpha(1)beta(1)gamma(2S) receptors (vol 94, pg 491, 2005) (Errartum)', Journal of Neurochemistry, 97 302-302 (2006) [C3]
DOI 10.1111/j.1471-4159.2005.03240.x
Citations Scopus - 10Web of Science - 10
2005 Haarmann CS, Dulhunty AF, Laver DR, 'Regulation of skeletal ryanodine receptors by dihydropyridine receptor II-III loop C-region peptides: relief of Mg2+ inhibition', Biochemical Journal, 387 429-436 (2005) [C1]
DOI 10.1042/BJ20040786
Citations Scopus - 13Web of Science - 13
2005 Laver DR, 'Coupled calcium release channels and their regulation by luminal and cytosolic ions', European Biophysics Journal with Biophysics Letters, 34 359-368 (2005) [C1]
DOI 10.1007/s00249-005-0483-y
Citations Scopus - 20Web of Science - 19
2005 Lindquist CEL, Laver DR, Birnir B, 'The mechanism of SR95531 inhibition at GABA(A) receptors examined in human alpha(1)beta(1) and alpha(1)beta(1)gamma(2S) receptors', Journal of Neurochemistry, 94 491-501 (2005) [C1]
2005 Beard NA, Casarotto MG, Wei L, Varsanyi M, Laver DR, Dulhunty AF, 'Regulation of ryanodine receptors by calsequestrin: Effect of high luminal Ca2+ and phosphorylation', Biophysical Journal, 88 3444-3454 (2005) [C1]
DOI 10.1529/biophysj.104.051441
Citations Scopus - 76Web of Science - 71
2004 Laver DR, O'Neill ER, Lamb GD, 'Luminal Ca2+ - regulated Mg2+ inhibition of skeletal RyRs reconstituted as isolated channels or coupled clusters', J Gen Physiol, 124 741-758 (2004) [C1]
DOI 10.1085/jgp.200409092
Citations Scopus - 54Web of Science - 55
2004 Beard NA, Laver DR, Dulhunty AF, 'Calsequestrin and the calcium release challen of skeletal and cardiac muscle', Progress in Biophysics & Molecular Biology, 85 33-69 (2004) [C1]
DOI 10.1016/j.pbiomolbio.2003.07.001
Citations Scopus - 177Web of Science - 164
2003 O'Neill ER, Sakowska MM, Laver DR, 'Regulation of the Calcium Release Channel from Skeletal Muscle by Suramin and the Disulfonated Stilbene Derivatives DIDS, DBDS, and DNDS', Biophysical Journal, 84 1674-1689 (2003) [C1]
DOI 10.1016/S0006-3495(03)74976-5
Citations Scopus - 27Web of Science - 26
2003 Honen BN, Saint DA, Laver DR, 'Supression of Calcium Sparks in Rat Ventricular Myocytes and Direct Inhitition of Sheep Cardiac RyR Channels by EPA, DHA and Oleic Acid', Journal of Membrane Biology, 196 95-103 (2003) [C1]
DOI 10.1007/s00232-003-0628-9
Citations Scopus - 44Web of Science - 41
2003 Haarmann C, Green D, Casarotto MG, Laver DR, Dalhunty AF, 'The Random-Coil 'C' fragment of the dihydropyridine receptor II-III loop can activate or inhibit native skeletal ryanodine receptors', Biochemical journal, 375 305-316 (2003) [C1]
DOI 10.1042/BJ20021763
Citations Scopus - 32Web of Science - 32
2002 Dulhunty AF, Haarmann CS, Green D, Laver DR, Board PG, Casarotto MG, 'Interactions between dihydropyridine receptors and ryanodine receptors in striated muscle', PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, 79 45-75 (2002)
DOI 10.1016/S0079-6107(02)00013-5
Citations Scopus - 59Web of Science - 64
2002 Beard NA, Sakowska MM, Dulhunty AF, Laver DR, 'Calsequestrin is an inhibitor of skeletal muscle ryanodine receptor calcium release channels', Biophysical Journal, 82 310-320 (2002)

We provide novel evidence that the sarcoplasmic reticulum calcium binding protein, calsequestrin, inhibits native ryanodine receptor calcium release channel activity. Calsequestri... [more]

We provide novel evidence that the sarcoplasmic reticulum calcium binding protein, calsequestrin, inhibits native ryanodine receptor calcium release channel activity. Calsequestrin dissociation from junctional face membrane was achieved by increasing luminal (trans) ionic strength from 250 to 500 mM with CsCl or by exposing the luminal side of ryanodine receptors to high [Ca 2+ ] (13 mM) and dissociation was confirmed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Calsequestrin dissociation caused a 10-fold increase in the duration of ryanodine receptor channel opening in lipid bilayers. Adding calsequestrin back to the luminal side of the channel after dissociation reversed this increased activity. In addition, an anticalsequestrin antibody added to the luminal solution reduced ryanodine receptor activity before, but not after, calsequestrin dissociation. A population of ryanodine receptors ("35%) may have initially lacked calsequestrin, because their activity was high and was unaffected by increasing ionic strength or by anticalsequestrin antibody: their activity fell when purified calsequestrin was added and they then responded to antibody. In contrast to native ryanodine receptors, purified channels, depleted of triadin and calsequestrin, were not inhibited by calsequestrin. We suggest that calsequestrin reduces ryanodine receptor activity by binding to a coprotein, possibly to the luminal domain of triadin.

Citations Scopus - 101
2002 Beard NA, Sakowska MM, Dulhunty AF, Laver DR, 'Calsequestrin is an Inhibitor of Skeletal Muscle Ryanodine Receptor Calcium Release Channels', Biophysical Journal, 82 310-320 (2002) [C1]
Citations Web of Science - 96
2001 Dulhunty AF, Laver D, Curtis SM, Pace S, Haarmann C, Gallant EM, 'Characteristics of irreversible ATP activation suggest that native skeletal ryanodine receptors can be phosphorylated via an endogenous CaMKII', BIOPHYSICAL JOURNAL, 81 3240-3252 (2001)
Citations Scopus - 39Web of Science - 37
2001 Laver DR, Lenz GKE, Dulhunty AF, 'Phosphate ion channels in sarcoplasmic reticulum of rabbit skeletal muscle', JOURNAL OF PHYSIOLOGY-LONDON, 535 715-728 (2001)
DOI 10.1111/j.1469-7793.2001.t01-1-00715.x
Citations Web of Science - 19
2001 Laver DR, Lenz GKE, Lamb GD, 'Regulation of the calcium release channel from rabbit skeletal muscle by the nucleotides ATP, AMP, IMP and adenosine', JOURNAL OF PHYSIOLOGY-LONDON, 537 763-778 (2001)
Citations Web of Science - 43
2001 Laver DR, 'The power of single channel recording and analysis: Its application to ryanodine receptors in lipid bilayers', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 28 675-686 (2001)
DOI 10.1046/j.1440-1681.2001.03503.x
Citations Scopus - 7Web of Science - 9
2000 Laver DR, Eager KR, Taoube L, Lamb GD, 'Effects of cytoplasmic and luminal pH on Ca2+ release channels from rabbit skeletal muscle', BIOPHYSICAL JOURNAL, 78 1835-1851 (2000)
Citations Scopus - 24Web of Science - 24
2000 Lamb GD, Laver DR, Stephenson DG, 'Perspective - Questions about adaptation in ryanodine receptors', JOURNAL OF GENERAL PHYSIOLOGY, 116 883-890 (2000)
DOI 10.1085/jgp.116.6.883
Citations Web of Science - 11
2000 Panter S, Thomson R, de Bruxelles G, Laver D, Trevaskis B, Udvardi M, 'Identification with proteomics of novel proteins associated with the peribacteroid membrane of soybean root nodules', MOLECULAR PLANT-MICROBE INTERACTIONS, 13 325-333 (2000)
DOI 10.1094/MPMI.2000.13.3.325
Citations Scopus - 100Web of Science - 92
1999 Dulhunty AF, Laver DR, Gallant EM, Casarotto MG, Pace SM, Curtis S, 'Activation and inhibition of skeletal RyR channels by a part of the skeletal DHPR II-III loop: Effects of DHPR Ser(687) and FKBP12', BIOPHYSICAL JOURNAL, 77 189-203 (1999)
DOI 10.1016/S0006-3495(99)76881-5
Citations Scopus - 66Web of Science - 73
1998 Ahern GP, Laver DR, 'ATP inhibition and rectification of a Ca2+-activated anion channel in sarcoplasmic reticulum of skeletal muscle', BIOPHYSICAL JOURNAL, 74 2335-2351 (1998)
Citations Scopus - 21Web of Science - 23
1998 Laver DR, Lamb GD, 'Inactivation of Ca2+ release channels (ryanodine receptors RyR1 and RyR2) with rapid steps in [Ca2+] and voltage', BIOPHYSICAL JOURNAL, 74 2352-2364 (1998)
Citations Scopus - 46Web of Science - 49
1997 Laver DR, Owen VJ, Junankar PR, Taske NL, Dulhunty AF, Lamb GD, 'Reduced inhibitory effect of Mg2+ on ryanodine receptor Ca2+ release channels in malignant hyperthermia', BIOPHYSICAL JOURNAL, 73 1913-1924 (1997)
Citations Scopus - 77Web of Science - 80
1997 Laver DR, Owen VJ, Junankar PR, Taske NL, Dulhunty AF, Lamb GD, 'Ca2+- and Mg2+-Regulation of Calcium Release Channels from Normal and Malignant Hyperthermia Susceptible Pigs', Biophysical Journal, 73 1913-1924 (1997) [C1]
1997 McCulloch SR, Laver DR, Walker NA, 'Anion channel activity in the Chara plasma membrane: Co-operative subunit phenomena and a model', JOURNAL OF EXPERIMENTAL BOTANY, 48 383-397 (1997)
DOI 10.1093/jxb/48.Special_Issue.383
Citations Web of Science - 8
1997 Laver DR, Cherry CA, Walker NA, 'The actions of calmodulin antagonists W-7 and TFP and of calcium on the gating kinetics of the calcium-activated large conductance potassium channel of the Chara protoplasmic drop: A substate-sensitive analysis', JOURNAL OF MEMBRANE BIOLOGY, 155 263-274 (1997)
DOI 10.1007/s002329900179
Citations Scopus - 19Web of Science - 17
1997 Laver DR, Baynes TM, Dulhunty AF, 'Magnesium inhibition of ryanodine-receptor calcium channels: Evidence for two independent mechanisms', JOURNAL OF MEMBRANE BIOLOGY, 156 213-229 (1997)
DOI 10.1007/s002329900202
Citations Scopus - 144Web of Science - 151
1997 Laver DR, Gage PW, 'Interpretation of substates in ion channels: Unipores or multipores?', PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, 67 99-140 (1997)
DOI 10.1016/S0079-6107(97)00008-4
Citations Web of Science - 19
1996 Dulhunty AF, Junankar PR, Eager KR, Ahern GP, Laver DR, 'Ion channels in the sarcoplasmic reticulum of striated muscle', ACTA PHYSIOLOGICA SCANDINAVICA, 156 375-385 (1996)
DOI 10.1046/j.1365-201X.1996.193000.x
Citations Scopus - 27Web of Science - 24
1996 Kourie JI, Laver DR, Junankar PR, Gage PW, Dulhunty AF, 'Characteristics of two types of chloride channel in sarcoplasmic reticulum vesicles from rabbit skeletal muscle', BIOPHYSICAL JOURNAL, 70 202-221 (1996)
Citations Scopus - 55Web of Science - 58
1996 Laver D, Curtis B, 'Rapid solution change activates ryanodine receptors within 20 ms.', BIOPHYSICAL JOURNAL, 70 WPO48-WPO48 (1996)
1996 Laver DR, Curtis BA, 'Surface potentials measure ion concentrations near lipid bilayers during rapid solution changes', BIOPHYSICAL JOURNAL, 71 722-731 (1996)
Citations Scopus - 11Web of Science - 10
1996 Laver DR, Curtis BA, 'Response of ryanodine receptor channels to Ca2+ steps produced by rapid solution', BIOPHYSICAL JOURNAL, 71 732-741 (1996)
Citations Scopus - 31Web of Science - 33
1996 Kourie JI, Laver DR, Ahern GP, Dulhunty AF, 'A calcium-activated chloride channel in sarcoplasmic reticulum vesicles from rabbit skeletal muscle', AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 270 C1675-C1686 (1996)
Citations Web of Science - 31
1996 Kourie JI, Laver DR, Ahern GP, Dulhunty AF, 'A calcium-activated chloride channel in sarcoplasmic reticulum vesicles from rabbit skeletal muscle', American Journal of Physiology - Cell Physiology, 270 (1996)

A Ca 2+ -activated Cl - channel is described in sarcoplasmic reticulum (SR) enriched vesicles of skeletal muscle incorporated into lipid bilayers. Small chloride (SCl) channels... [more]

A Ca 2+ -activated Cl - channel is described in sarcoplasmic reticulum (SR) enriched vesicles of skeletal muscle incorporated into lipid bilayers. Small chloride (SCl) channels (n = 20) were rapidly and reversibly activated when cis- (cytoplasmic) [Ca 2+ ] was increased above 10 -7 M, with trans- (luminal) [Ca 2+ ] at either 10 -3 or 10 -7 M. The open probability of single channels increased from zero when cis-[Ca 2+ ] was 10 -7 M to 0.61 ± 0.12 when [Ca 2+ ] was 10 -4 M. High- and low- conductance levels in single- channel activity were activated at different cis-[Ca 2+ ]. Channel openings to the maximum conductance, 65-75 pS (250/50 mM Cl - , cis/trans), were active when cis-[Ca 2+ ] was increased above 5 x 10 -6 M. In contrast to the maximum conductance, channel openings to submaximal levels between 5 and 40 pS were activated at a lower cis-[Ca 2+ ] and dominated channel activity between 5 x 10 -7 and 5 x 10 -6 M. Activation of SCl channels was Ca 2+ specific and not reproduced by cytoplasmic Mg 2+ concentrations of 10 -3 M. We suggest that the SCl channel arises in the SR membrane. The Ca 2+ dependence of this channel implies that it is active at [Ca 2+ ] achieved during muscle contraction.

Citations Scopus - 33
1995 Laver DR, Roden LD, Ahem GP, Eager KR, Junankar PR, Dulhunty AF, 'Cytoplasmic Ca2+ Inhibits the Ryanodine Receptor from Cardiac Muscle', Journal of Membrane Biology, 147 7-22 (1995) [C1]
Citations Scopus - 133Web of Science - 130
1994 Laver DR, 'The barrel-stave model as applied to alamethicin and its analogs reevaluated', Biophysical Journal, 66 355-359 (1994)

Alamethicin and its analogs from cation selective, multi-conductance channels in lipid bilayers. The conductance levels have been thought to be due to a barrel-stave structure whe... [more]

Alamethicin and its analogs from cation selective, multi-conductance channels in lipid bilayers. The conductance levels have been thought to be due to a barrel-stave structure where conducting pores (barrels) are formed by the self-assembly of a variable number of alpha-helical rods (staves). The conductance transitions were then interpreted as the addition or deletion of peptide monomers from the pore-forming complex (Sansom, M.S. 1991. Prog. Biophys. Mol. Biol. 55:139¿235). Initially, pore conductances were calculated from that expected of right circular cylinders of "bulk" electrolyte. More recent theories also included the access resistance of the electrolyte outside the pore. However, they all consistently overestimated the observed conductances. The reason for the discrepancy is presented here. Previous theories ignored the effects of ion concentration gradients near the pore. Hence, they only held in the limit of small bilayer potentials ( < 25 mV) and so would overestimate measurements that typically used much larger potentials ( > 100 mV). This theoretical flaw is corrected by using Läuger's theory of diffusion-limited ion flow (Läuger, P. 1976. Biochim. Biophys. Acta. 455:493¿509). Thus, including the effects of ion concentration gradients results in a considerable improvement in predicting pore conductances. It is found that: 1) the effects of ion concentration gradients must be included in the barrel-stave model for it to apply to the available data; 2) previously published explanations for the discrepancy between the model and the data, namely the "distorted bundle" and the "head-to-tail aggregate" hypotheses are not necessary (reviewed by Sansom, 1991). © 1994, The Biophysical Society. All rights reserved.

DOI 10.1016/S0006-3495(94)80784-2
Citations Scopus - 30
1994 LAVER DR, 'THE BARREL-STAVE MODEL AS APPLIED TO ALAMETHICIN AND ITS ANALOGS REEVALUATED', BIOPHYSICAL JOURNAL, 66 355-359 (1994)
Citations Web of Science - 24
1994 LAVER DR, FAIRLEYGRENOT KA, 'SURFACE-POTENTIALS NEAR THE MOUTH OF THE LARGE-CONDUCTANCE K+ CHANNEL FROM CHARA-AUSTRALIS - A NEW METHOD OF TESTING FOR DIFFUSION-LIMITED ION FLOW', JOURNAL OF MEMBRANE BIOLOGY, 139 149-165 (1994)
Citations Scopus - 10Web of Science - 10
1992 LAVER DR, 'DIVALENT-CATION BLOCK AND COMPETITION BETWEEN DIVALENT AND MONOVALENT CATIONS IN THE LARGE-CONDUCTANCE K+ CHANNEL FROM CHARA-AUSTRALIS', JOURNAL OF GENERAL PHYSIOLOGY, 100 269-300 (1992)
DOI 10.1085/jgp.100.2.269
Citations Scopus - 23Web of Science - 23
1991 LAVER DR, WALKER NA, 'ACTIVATION BY CA2+ AND BLOCK BY DIVALENT IONS OF THE K+-CHANNEL IN THE MEMBRANE OF CYTOPLASMIC DROPS FROM CHARA-AUSTRALIS', JOURNAL OF MEMBRANE BIOLOGY, 120 131-139 (1991)
DOI 10.1007/BF01872396
Citations Scopus - 30Web of Science - 32
1991 FAIRLEY K, LAVER D, WALKER NA, 'WHOLE-CELL AND SINGLE-CHANNEL CURRENTS ACROSS THE PLASMALEMMA OF CORN SHOOT SUSPENSION CELLS', JOURNAL OF MEMBRANE BIOLOGY, 121 11-22 (1991)
DOI 10.1007/BF01870647
Citations Scopus - 24Web of Science - 29
1991 LAVER DR, 'A SURGICAL METHOD FOR ACCESSING THE PLASMAMEMBRANE OF CHARA-AUSTRALIS', PROTOPLASMA, 161 79-84 (1991)
DOI 10.1007/BF01322720
Citations Scopus - 18Web of Science - 22
1990 LAVER DR, 'COUPLING OF K+-GATING AND PERMEATION WITH CA-2+ BLOCK IN THE CA-2+-ACTIVATED K+ CHANNEL IN CHARA-AUSTRALIS', JOURNAL OF MEMBRANE BIOLOGY, 118 55-67 (1990)
DOI 10.1007/BF01872204
Citations Scopus - 22Web of Science - 24
1990 GENTLE IR, LAVER DR, RITCHIE GLD, 'TEMPERATURE AND PRESSURE-DEPENDENCE OF THE ELECTROOPTICAL KERR EFFECT OF SULFUR-DIOXIDE', JOURNAL OF PHYSICAL CHEMISTRY, 94 3434-3437 (1990)
DOI 10.1021/j100372a016
Citations Scopus - 17Web of Science - 16
1989 LAVER DR, FAIRLEY KA, WALKER NA, 'ION PERMEATION IN A K+ CHANNEL IN CHARA-AUSTRALIS - DIRECT EVIDENCE FOR DIFFUSION LIMITATION OF ION FLOW IN A MAXI-K CHANNEL', JOURNAL OF MEMBRANE BIOLOGY, 108 153-164 (1989)
DOI 10.1007/BF01871026
Citations Scopus - 25Web of Science - 30
1989 CRAVEN IE, HESLING MR, LAVER DR, LUKINS PB, RITCHIE GLD, VRBANCICH J, 'POLARIZABILITY ANISOTROPY, MAGNETIC-ANISOTROPY, AND QUADRUPOLE-MOMENT OF CYCLOHEXANE', JOURNAL OF PHYSICAL CHEMISTRY, 93 627-631 (1989)
DOI 10.1021/j100339a026
Citations Scopus - 37Web of Science - 44
1989 GENTLE IR, LAVER DR, RITCHIE GLD, '2ND HYPERPOLARIZABILITY AND STATIC POLARIZABILITY ANISOTROPY OF CARBON-DIOXIDE', JOURNAL OF PHYSICAL CHEMISTRY, 93 3035-3038 (1989)
DOI 10.1021/j100345a033
Citations Scopus - 17Web of Science - 22
1987 LAVER DR, WALKER NA, 'STEADY-STATE VOLTAG-DEPENDENT GATING AND CONDUCTION KINETICS OF SINGLE K+ CHANNELS IN THE MEMBRANE OF CYTOPLASMIC DROPS OF CHARA-AUSTRALIS', JOURNAL OF MEMBRANE BIOLOGY, 100 31-42 (1987)
DOI 10.1007/BF02209138
Citations Scopus - 34Web of Science - 43
1986 COSTER HGL, LAVER DR, 'THE EFFECT OF TEMPERATURE ON LIPID NORMAL-ALKANE INTERACTIONS IN LIPID BILAYERS', BIOCHIMICA ET BIOPHYSICA ACTA, 857 95-104 (1986)
DOI 10.1016/0005-2736(86)90102-1
Citations Scopus - 12Web of Science - 11
1986 COSTER HGL, LAVER DR, 'THE EFFECT OF BENZYL ALCOHOL AND CHOLESTEROL ON THE ACYL CHAIN ORDER AND ALKANE SOLUBILITY OF BIMOLECULAR PHOSPHATIDYLCHOLINE MEMBRANES', BIOCHIMICA ET BIOPHYSICA ACTA, 861 406-412 (1986)
DOI 10.1016/0005-2736(86)90448-7
Citations Scopus - 20Web of Science - 19
1985 SMITH JR, COSTER HGL, LAVER DR, 'THE DEPENDENCE OF THE CONDUCTANCE OF PHOSPHATIDYLCHOLINE BILAYERS UPON THE CONCENTRATION AND COMPOSITION OF THE EXTERNAL ELECTROLYTE', BIOCHIMICA ET BIOPHYSICA ACTA, 812 181-192 (1985)
DOI 10.1016/0005-2736(85)90537-1
Citations Scopus - 16Web of Science - 18
1985 LUKINS PB, LAVER DR, BUCKINGHAM AD, RITCHIE GLD, 'COTTON-MOUTON EFFECT, MAGNETIC-ANISOTROPY, AND CHARGE-DISTRIBUTION OF CYCLOPROPANE', JOURNAL OF PHYSICAL CHEMISTRY, 89 1309-1312 (1985)
DOI 10.1021/j100253a050
Citations Scopus - 19Web of Science - 29
1984 LAVER DR, SMITH JR, COSTER HGL, 'THE THICKNESS OF THE HYDROPHOBIC AND POLAR-REGIONS OF GLYCEROL MONOOLEATE BILAYERS DETERMINED FROM THE FREQUENCY-DEPENDENCE OF BILAYER CAPACITANCE', BIOCHIMICA ET BIOPHYSICA ACTA, 772 1-9 (1984)
DOI 10.1016/0005-2736(84)90511-X
Citations Scopus - 31Web of Science - 27
1984 SMITH JR, LAVER DR, COSTER HGL, 'THE CONDUCTANCE OF LECITHIN BILAYERS - THE DEPENDENCE UPON TEMPERATURE', CHEMISTRY AND PHYSICS OF LIPIDS, 34 227-236 (1984)
DOI 10.1016/0009-3084(84)90057-4
Citations Scopus - 28Web of Science - 31
1983 ASHCROFT RG, COSTER HGL, LAVER DR, SMITH JR, 'THE EFFECTS OF CHOLESTEROL INCLUSION ON THE MOLECULAR-ORGANIZATION OF BIMOLECULAR LIPID-MEMBRANES', BIOCHIMICA ET BIOPHYSICA ACTA, 730 231-238 (1983)
DOI 10.1016/0005-2736(83)90338-3
Citations Scopus - 46Web of Science - 53
1982 COSTER HGL, LAVER DR, SCHOENBORN BP, 'EFFECT OF 2H2O/H2O REPLACEMENT ON THE DIELECTRIC STRUCTURE OF LIPID BILAYER-MEMBRANES', BIOCHIMICA ET BIOPHYSICA ACTA, 686 141-143 (1982)
DOI 10.1016/0005-2736(82)90161-4
Citations Scopus - 4Web of Science - 7
Show 94 more journal articles

Conference (55 outputs)

Year Citation Altmetrics Link
2017 Gomez-Hurtado N, Walweel K, Laver D, Knollmann BC, 'Calmodulin Regulation of Ryanodine Receptors (RyR2) Depends on RyR2 Phosphorylation at Residues S2808 and S2814', BIOPHYSICAL JOURNAL (2017)
2017 Laver DR, Kong CH, Cannell MB, 'Modelling Calcium-Induced-Calcium-Release from Measurements of RyR Gating', BIOPHYSICAL JOURNAL (2017)
2016 Stoddard JG, Welsh JS, Laver DR, 'A Parallel Modelling Algorithm for Simulating Calcium Release in Cells', Proceedings. 6th IFAC Conference on Foundations of Systems Biology in Engineering (2016) [E1]
DOI 10.1016/j.ifacol.2016.12.107
Co-authors James Welsh
2016 Martin K, Johnstone D, Dosen P, Graham R, van Helden D, Kerr KP, et al., 'Assessment of cardiac functional changes in response to iron loading mouse models of genetic haemochromatosis' (2016)
Co-authors Dirk Vanhelden, Liz Milward, Karen Kerr
2016 Martin K, Johnstone D, Dosen P, Graham R, Van Helden D, Kerr KP, et al., 'Cardiac iron loading and pacemaker activity in two mouse models of genetic haemochromatosis' (2016)
Co-authors Dirk Vanhelden, Liz Milward, Karen Kerr
2016 Martin K, Johnstone D, Dosen P, Graham R, Liu J, Van helden D, et al., 'Increased iron loading in mouse models of genetic haemochromatosis and the assessment of cardiac function' (2016)
Co-authors Dirk Vanhelden, Karen Kerr, Liz Milward
2016 Martin K, Johnstone D, Graham R, Van Helden D, Kerr KP, Hollins S, et al., 'Alterations in cardiac iron status, electrophysiological responses and transcript levels in mouse models of dietary and genetic iron loading' (2016)
Co-authors Karen Kerr, Liz Milward, Dirk Vanhelden
2016 Ottesen AH, Laver DR, Omland T, Christensen G, Rosjo H, Louch WE, 'Secretoneurin, a novel endogenous CaMKIId inhibitor, inhibits Ca2+-dependent arrhythmogenesis', EUROPEAN HEART JOURNAL (2016)
2016 Nikolaev YA, Rohde PR, Laver DR, Martinac B, 'Mechanosensitivity of TRPC6 Ion Channel Reconstituted in the Liposomes', BIOPHYSICAL JOURNAL (2016)
2016 Oo YW, Imtiaz MS, vanHelden DF, Laver DR, 'Dantrolene Inhibition of Skeletal Muscle RYR in the Presence of CAM', BIOPHYSICAL JOURNAL (2016)
Co-authors Dirk Vanhelden
2016 Laver DR, Walweel K, Oo YW, van Helden D, dos Remedios C, Molenaar P, 'Calmodulin Regulation of Ryanodine Receptors (RyR2) Differs in Failing and Non-Faling Human Hearts due to Differences in RyR2 Phosphorylation', BIOPHYSICAL JOURNAL (2016)
Co-authors Dirk Vanhelden
2016 Nikolaev YA, Dosen PJ, Laver DR, Van Helden DF, Hamill OP, 'Biophysical Factors that Promote Mechanically-Induced Action Potentials in Neocortical and Hippocampal Pyramidal Neurons', BIOPHYSICAL JOURNAL (2016)
Co-authors Dirk Vanhelden
2015 Martin K, Johnstone D, Graham R, Van Helden D, Kerr KP, Hollins S, et al., 'The effects of iron loading on electrophysiological responses and transcript levels in dietary or genetic mouse models.' (2015) [E3]
Co-authors Dirk Vanhelden, Karen Kerr, Liz Milward
2015 Laver DR, Imtiaz MS, 'Influence of RyR2 Inhibition Kinetics on Calcium Sparks and Waves in a 3D Model of a Cardiac Cell', BIOPHYSICAL JOURNAL (2015) [E3]
2015 Vincze J, Dienes B, Szentesi P, Csernoch L, Laver DR, 'Effects of Triad Geometry and RyR Gating Scheme on Simulated Skeletal Muscle Sparks', BIOPHYSICAL JOURNAL (2015) [E3]
2015 Gomez-Hurtado N, Oo YW, Laver D, Knollmann BC, 'Calmodulin Potentiates RyR2 Block and Ca Wave Suppression by Flecainide', BIOPHYSICAL JOURNAL (2015) [E3]
2015 Nikolaev YA, Rohde PR, Cox CD, Laver DR, Martinac B, 'Mechanosensitivity of TRPC6 Ion Channels', BIOPHYSICAL JOURNAL (2015) [E3]
Citations Web of Science - 1
2015 Oo YW, Gomez-Hurtado N, vanHelden DF, Imtiaz MS, Knollmann BC, Laver DR, 'Dantrolene Inhibition of RyR2 requires Calmodulin', BIOPHYSICAL JOURNAL (2015) [E3]
Co-authors Dirk Vanhelden
2014 Laver DR, Cannell MB, Imtiaz MS, 'Anti-Arrhythmic Block of Ryr2 by Flecainide Versus Pro-Arrhythmic Block by Tetracaine in a 3D Model of a Cardiac Cell', BIOPHYSICAL JOURNAL (2014) [E3]
2014 Walweel KD, vanHelden DF, Imtiaz MS, Dos Remedios C, Molenaar P, Laver DR, 'Inhibition of RyR2 from Failing and Non-Failing Human Hearts by Calmodulin', BIOPHYSICAL JOURNAL (2014) [E3]
Co-authors Dirk Vanhelden
2014 Cannell MB, Kong CHT, Laver DR, 'Ryanodine receptor cluster organisation and consequences for EC coupling', CARDIOVASCULAR RESEARCH (2014) [E3]
DOI 10.1093/cvr/cvu091.74
2013 Laver DR, Kong CHT, Imtiaz MS, Cannell MB, 'Termination of Calcium Sparks: An Emergent Property from Stochastic RyR Gating and Dyad Geometry', BIOPHYSICAL JOURNAL (2013) [E3]
2013 Van Heiden DF, Laver DR, Imtiaz MS, Hashitani H, 'Cellular Interactions Controlling Tonic and Peristaltic Contractions of Gastric Smooth Muscle', JOURNAL OF PHYSIOLOGICAL SCIENCES (2013) [E3]
Co-authors Dirk Vanhelden
2012 Imtiaz MS, Van Helden DF, Laver DR, 'Three-dimensional modeling of Ca2+ dynamics in single cardiac cells', Sydney 2012 Joint AuPS/PSNZ/ASB Meeting. Programme (2012) [E3]
Co-authors Dirk Vanhelden
2012 Imtiaz MS, Allen DG, Van Helden DF, Laver DR, 'Role of intracellular Ca2+ in sinoatrial node pacemaking', Sydney 2012 Joint AuPS/PSNZ/ASB Meeting. Programme (2012) [E3]
Co-authors Dirk Vanhelden
2012 Mehra DR, Van Helden DF, Laver DR, 'Role of cardiac Na+ channel blockers and Mg2+ in inhibiting the cardiac calcium release channel', Sydney 2012 Joint AuPS/PSNZ/ASB Meeting. Programme (2012) [E3]
Co-authors Dirk Vanhelden
2012 Walweel K, Beard NA, Li J, Van Helden DF, Imtiaz MS, Molenaar P, Laver DR, 'Regulation of human RYR2 by intracellular Ca2+ and Mg2+', Sydney 2012 Joint AuPS/PSNZ/ASB Meeting. Programme (2012) [E3]
Co-authors Dirk Vanhelden
2012 Li J, Imtiaz MS, Beard NA, Dulhunty AF, Thorne RF, Van Helden DF, Laver DR, 'Adrenergic stimulation increases RYR2 activity via intracellular Ca2+ and Mg2+ regulation', Sydney 2012 Joint AuPS/PSNZ/ASB Meeting. Programme (2012) [E3]
Citations Scopus - 14Web of Science - 12
Co-authors Dirk Vanhelden, Rick Thorne
2012 Li J, Imtiaz MS, Beard NA, Dulhunty AF, Thorne RF, Van Helden DF, Laver DR, 'Adrenergic stimulation alters RyR2 regulation by Ca2+ and Mg2+', Heart, Lung and Circulation: Abstracts of ISHR Auckland Workshop (2012) [E3]
Co-authors Rick Thorne, Dirk Vanhelden
2011 Li J, Beard NA, Dulhunty AF, vanHelden DF, Laver DR, 'The Effect of Adrenergic Stimulation on the Calcium Release Channel', BIOPHYSICAL JOURNAL (2011) [E3]
Co-authors Dirk Vanhelden
2011 Laver DR, vanHelden DF, 'Tetracaine Inhibits RyRs by Three Mechanisms', BIOPHYSICAL JOURNAL (2011) [E3]
Co-authors Dirk Vanhelden
2011 Mehra DR, vanHelden DF, Knollmann BC, Laver DR, 'Inhibition of Cardiac Ca2+ Release Channels by Class I Anti Arrhythmic Drugs as Therapy for Arrhythmia', BIOPHYSICAL JOURNAL (2011) [E3]
Co-authors Dirk Vanhelden
2011 Walweel K, Li J, Van Helden DF, Imtiaz MS, Molenaar P, Laver DR, 'Regulation of RyRs by intracellular Ca2+ and Mg2+ compared in sheep, rat and human heart', Proceedings of the Australian Physiological Society 2011 (2011) [E3]
Co-authors Dirk Vanhelden
2011 Mehra DR, Van Helden DF, Hwang HS, Knollmann B, Laver DR, 'Role of cardiac Na+ channel blockers in inhibiting the cardiac calcium release channel', Proceedings of the Australian Physiological Society 2011 (2011) [E3]
Co-authors Dirk Vanhelden
2011 Morris D, Saint D, Laver DR, 'Negative inotropic effect of riluzole: Blockade of the ryanadine receptor?', Heart, Lung and Circulation (2011) [E3]
2009 Hollins SL, Johnstone DM, Graham R, Van Helden DF, Kerr KP, Laver DR, et al., 'Cardiac gene expression in mouse models of iron loading disorders', 2009 International Biolron Society Meeting: Program Book (2009) [E3]
Co-authors Liz Milward, Rodney Scott, Dirk Vanhelden, Karen Kerr
2009 Mehra DR, Van Helden DF, Knollmann B, Laver DR, 'Flecainide inhibits CPVT induced cardiac arrhythmias by open state block of ryanodine receptor Ca2+ release channels and reduction of Ca2+ spark mass', 33rd Annual Meeting of the Australian Society for Biophysics: Program (2009) [E3]
Co-authors Dirk Vanhelden
2009 Hollins SL, Johnstone DM, Van Helden DF, Kerr KP, Laver DR, Metelerkamp KM, et al., 'Cardiac gene expression in mouse models of iron loading', ASMR XVII NSW Scientific Meeting: Programme and Abstracts (2009) [E3]
Co-authors Karen Kerr, Dirk Vanhelden, Rodney Scott, Liz Milward
2009 Laver DR, Quail AW, Sitsapesan H, Van Helden DF, 'The effect of volatile anaesthetics on the cardiac ryanodine receptor', Biophysical Journal (2009) [E3]
Co-authors Dirk Vanhelden, Tony Quail
2009 Hilliard FA, Laver DR, Le Marchand SJ, Piston DW, Knollmann BG, 'Flecainide inhibits arrhythmogenic Ca2+ waves by open state block of ryanodine receptor Ca2+ release channels and reduction of Ca2+ spark mass', Circulation (2009) [E3]
2008 Laver DR, Quail AW, Sitsapesan H, Van Helden DF, 'Effect of volatile anaesthetics on the calcium release channel in the heart', Proceedings of the Australian Physiological Society (2008) [E3]
Co-authors Dirk Vanhelden, Tony Quail
2008 Van Helden DF, Laver DR, Imtiaz MS, 'Ca2+ phase waves: A fundamental mechanism underlying propagation of gastric slow waves', Proceedings of the Australian Physiological Society (2008) [E3]
Co-authors Dirk Vanhelden
2008 Chopra N, Watanabe H, Laver DR, Hwang HS, Roden DM, Knollmann BC, 'Flecainide blocks cardiac ryanodine channels and prevents catecholaminergic ventricular tachycardia in cardiac calsequestrin null mice', Circulation (2008) [E3]
2007 Tierney ML, Everitt AB, Seymour VAL, Laver DR, 'Subunit-specific interactions between gabaa receptors underlie diazepam modulated high conductance gaba channels (Poster)', 7th IBRO 2007 World Congress of Neuroscience Program (2007) [E3]
2007 Chopra N, Laver DR, Watanabe H, Nair UB, Stein CM, Knollmann BC, 'Amitriptyline activates cardiac ryanodine receptors independently of its action on cardiac calsequestrin: Role for amitriptyline linked sudden cardiac death', Circulation (2007) [E3]
2007 Laver DR, 'Store activation mechanism for cardiac ryanodine receptors', BIOPHYSICAL JOURNAL (2007)
2005 Honen BN, Lamb GD, Laver DR, Ikemoto N, 'Aberrant calcium release underlying sudden cardiac death probed with RyR domain peptides', BIOPHYSICAL JOURNAL (2005)
2005 Laver DR, Lamb GD, 'Regulation of single and coupled RyRs in bilayers by luminal Ca2+', BIOPHYSICAL JOURNAL (2005)
2005 Honen BN, Dalton RL, Van Helden DF, Laver DR, 'Acute application of n-3 polyunsaturated fatty acids modify calcium sparks in permeabilised rat cardiac myocytes', Proceedings of the Australian Physiological Society (2005) [E3]
Co-authors Dirk Vanhelden
2005 Laver DR, 'Regulation of ryanodine receptors from skeletal and cardiac muscle by components of the cytoplasm and lumen', Proceedings of the Australian Physiological Society (2005) [E3]
2004 Honen BN, Saint DA, Van Helden DF, Laver DR, 'The effects of fatty acids on SR calcium release channels from cardiac muscle', Biophysical Journal (2004) [E3]
Co-authors Dirk Vanhelden
2004 Haarmann CS, Dulhunty AF, Laver DR, 'The manifold effects of peptide C region of the DHPR II-III loop on RyRs', Biophysical Journal (2004) [E3]
2003 O'Neill E, Lamb G, Laver D, 'Magnesium inhibition of skeletal RyRs modified by DIDS, ryanodine and ATP', BIOPHYSICAL JOURNAL (2003)
2003 Kobayashi S, Yamamoto T, Laver DR, Lamb GD, Ikemoto N, 'RyR1 and RyR2 seem to share a common mechanism of cytoplasmic domain-mediated channel regulation: peptide probe studies', BIOPHYSICAL JOURNAL (2003)
1997 McCulloch SR, Laver DR, Walker NA, 'Anion channel activity in the Chara plasma membrane: Co-operative subunit phenomena and a model', Journal of Experimental Botany (1997)

Anion channel activity in the plasma membrane of internodal cells of Chara australis has been studied using the patch clamp method and the records analysed with a program based on... [more]

Anion channel activity in the plasma membrane of internodal cells of Chara australis has been studied using the patch clamp method and the records analysed with a program based on the Hidden Markov Model. The activity was variable in time, and often showed very noisy periods. At other times there were one or more of five types of channel-like activity. These are believed, like the noise, to arise from the same anion-conducting mechanism in the membrane. The channel-like activity shows many current levels, the actual levels varying on a time-scale of the order of seconds. The records show non-independent transitions between levels, and thus the activity is not the result of the patch containing many independent channels. The currents often move sequentially between adjacent levels. The current levels are at times more closely spaced as the magnitude of the current increases. Underlying this sequential transition scheme it is found that current and conductance frequently show levels that are integer multiples of a unit. Typically about 10 levels occur, a typical transition scheme being (in units) 0 mutually implies 4 mutually implies 7 mutually implies 9. It is shown that it is possible to model such sequential transition schemes with underlying units by considering a new model based on a random walk on a semiregular fragmentary tessellation of a plane.

Citations Scopus - 9
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Grants and Funding

Summary

Number of grants 39
Total funding $3,273,613

Click on a grant title below to expand the full details for that specific grant.


20171 grants / $20,000

Regulation of cardiac ryanodine receptor (RyR2) channels by clinically ed hydandoin based drugs$20,000

Funding body: John Hunter Hospital Charitable Trust

Funding body John Hunter Hospital Charitable Trust
Project Team Professor Derek Laver, Doctor Nicholas Jackson
Scheme Research Grant
Role Lead
Funding Start 2017
Funding Finish 2017
GNo G1700265
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

20152 grants / $615,705

Regulation of RyR2 channels by calmodulin in healthy and diseased hearts$613,705

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Professor Derek Laver, Professor Dirk Van Helden, Associate Professor Bjorn Knollman
Scheme Project Grant
Role Lead
Funding Start 2015
Funding Finish 2018
GNo G1400064
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

Biophysical Society 59th Annual Meeting, Maryland USA, 7-11 Feb 2015$2,000

Funding body: University of Newcastle - Faculty of Health and Medicine

Funding body University of Newcastle - Faculty of Health and Medicine
Project Team Professor Derek Laver
Scheme Travel Grant
Role Lead
Funding Start 2015
Funding Finish 2016
GNo G1500429
Type Of Funding Internal
Category INTE
UON Y

20141 grants / $1,728

Biophysical Society 58th Annual Meeting, San Fransisco USA, 15-19 February 2014$1,728

Funding body: University of Newcastle - Faculty of Health and Medicine

Funding body University of Newcastle - Faculty of Health and Medicine
Project Team Professor Derek Laver
Scheme Travel Grant
Role Lead
Funding Start 2014
Funding Finish 2014
GNo G1400396
Type Of Funding Internal
Category INTE
UON Y

20132 grants / $12,000

Investigating the basis for diabetes-associated gastric motility disorders$10,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Dirk Van Helden, Professor Derek Laver
Scheme Near Miss Grant
Role Investigator
Funding Start 2013
Funding Finish 2013
GNo G1300485
Type Of Funding Internal
Category INTE
UON Y

Biophysical Society 57th Annual Meeting, Pennsylvania Convention Centre, Philadelphia, 2 - 6 February 2013$2,000

Funding body: University of Newcastle - Faculty of Health and Medicine

Funding body University of Newcastle - Faculty of Health and Medicine
Project Team Professor Derek Laver
Scheme Travel Grant
Role Lead
Funding Start 2013
Funding Finish 2013
GNo G1300542
Type Of Funding Internal
Category INTE
UON Y

20122 grants / $22,000

Gastric Slow Waves and Motility Disorders$20,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Dirk Van Helden, Professor Derek Laver
Scheme Near Miss Grant
Role Investigator
Funding Start 2012
Funding Finish 2012
GNo G1200674
Type Of Funding Internal
Category INTE
UON Y

Gordon Research Conference on Muscle, Les Diablerets Conference Center, Les Diablerets Switzerland, 3 - 8 June 2012$2,000

Funding body: University of Newcastle - Faculty of Health and Medicine

Funding body University of Newcastle - Faculty of Health and Medicine
Project Team Professor Derek Laver
Scheme Travel Grant
Role Lead
Funding Start 2012
Funding Finish 2012
GNo G1200933
Type Of Funding Internal
Category INTE
UON Y

20112 grants / $538,706

Ryanodine receptor inhibitors as therapy for Ca2+ store overload induced arrhythmias$536,706

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Professor Derek Laver, Professor Dirk Van Helden, Associate Professor Bjorn Knollman
Scheme Project Grant
Role Lead
Funding Start 2011
Funding Finish 2013
GNo G1000274
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

Biophysics Society, Baltimore Convention Centre, 5 - 9 March 2011$2,000

Funding body: University of Newcastle - Faculty of Health and Medicine

Funding body University of Newcastle - Faculty of Health and Medicine
Project Team Professor Derek Laver
Scheme Travel Grant
Role Lead
Funding Start 2011
Funding Finish 2011
GNo G1100184
Type Of Funding Internal
Category INTE
UON Y

20105 grants / $528,050

Regulation of calcium release channels (RyR2) in healthy and failing hearts$325,575

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Professor Derek Laver, Dr Nicole Beard, Professor Angela Dulhunty
Scheme Project Grant
Role Lead
Funding Start 2010
Funding Finish 2012
GNo G0190194
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

HMRI MRSP Infrastructure Grant (10-11) - Cardiovascular$76,117

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Professor Derek Laver, Professor Dirk Van Helden, Associate Professor Eugene Nalivaiko, Associate Professor Liz Milward, Professor Robert Callister, Professor Manohar Garg, Conjoint Professor Tony Quail
Scheme NSW MRSP Infrastructure Grant
Role Lead
Funding Start 2010
Funding Finish 2010
GNo G1100525
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

HMRI MRSP Infrastructure Grant 09/10 - Cardiovascular$62,358

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Professor Derek Laver
Scheme NSW MRSP Infrastructure Grant
Role Lead
Funding Start 2010
Funding Finish 2010
GNo G1000559
Type Of Funding Contract - Aust Non Government
Category 3AFC
UON Y

ABI 7500 Real Time PCR System $34,000

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Doctor Rick Thorne, Doctor Nikki Verrills, Professor Murray Cairns, Associate Professor Paul Tooney, Associate Professor Doug Smith, Professor Gordon Burns, Emeritus Professor Leonie Ashman, Conjoint Professor Keith Jones, Doctor Charles De Bock, Associate Professor Chris Dayas, Associate Professor Brett Graham, Doctor Martin Horan, Doctor Rebecca Lim, Doctor Severine Roselli, Doctor Larisa Bobrovskaya, Doctor Kathryn Skelding, Associate Professor Rohan Walker, Doctor Jude Weidenhofer, Professor Philip Bolton, Professor Alan Brichta, Professor Robert Callister, Professor Trevor Day, Associate Professor Phillip Dickson, Professor Manohar Garg, Doctor Phil Jobling, Professor Derek Laver, Associate Professor Eugene Nalivaiko, Emeritus Professor John Rostas
Scheme Equipment Grant
Role Investigator
Funding Start 2010
Funding Finish 2010
GNo G1000055
Type Of Funding Other Public Sector - Commonwealth
Category 2OPC
UON Y

Effective anti-arrhythmic drugs: How do they work?$30,000

Funding body: BellBerry Limited

Funding body BellBerry Limited
Project Team Professor Derek Laver, Professor Dirk Van Helden, Associate Professor Bjorn Knollman
Scheme Near Miss
Role Lead
Funding Start 2010
Funding Finish 2012
GNo G0900218
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y

20092 grants / $21,175

Propagation and directionality of gastric slow waves$20,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Dirk Van Helden, Professor Derek Laver
Scheme Near Miss Grant
Role Investigator
Funding Start 2009
Funding Finish 2009
GNo G0189817
Type Of Funding Internal
Category INTE
UON Y

Gordon Conference on Muscle, New Hampshire, USA, 14-19 June 2009$1,175

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Derek Laver
Scheme Travel Grant
Role Lead
Funding Start 2009
Funding Finish 2009
GNo G0900243
Type Of Funding Internal
Category INTE
UON Y

20082 grants / $27,500

The effects of iron status on calcium handling systems in heart and brain$25,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Professor Derek Laver, Associate Professor Liz Milward, Professor Dirk Van Helden, Laureate Professor Rodney Scott
Scheme Project Grant
Role Lead
Funding Start 2008
Funding Finish 2008
GNo G0188463
Type Of Funding Contract - Aust Non Government
Category 3AFC
UON Y

Biophysics Society, Long Beach Conference Centre, 2/2/2008 - 6/2/2008$2,500

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Derek Laver
Scheme Travel Grant
Role Lead
Funding Start 2008
Funding Finish 2008
GNo G0188597
Type Of Funding Internal
Category INTE
UON Y

20076 grants / $594,607

HMRI - Cardiovascular Research Program$518,556

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Professor Derek Laver, Conjoint Professor Tony Quail, Professor Dirk Van Helden, Professor Manohar Garg, Professor Robin Callister
Scheme NSW MRSP Infrastructure Grant
Role Lead
Funding Start 2007
Funding Finish 2009
GNo G0187946
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

High speed/sensitivity CCD camera$30,000

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Professor Dirk Van Helden, Professor Eileen McLaughlin, Professor Gordon Burns, Doctor Rick Thorne, Dr Marcus Howlett, Doctor Mohammad Imtiaz, Professor Alan Brichta, Professor Robert Callister, Associate Professor Brett Graham, Professor Derek Laver, Associate Professor Liz Milward, Doctor John Holdsworth
Scheme Equipment Grant
Role Investigator
Funding Start 2007
Funding Finish 2007
GNo G0188196
Type Of Funding Other Public Sector - Commonwealth
Category 2OPC
UON Y

Magnesium and calcium regulation of calcium release channels in cardiac and skeletal muscle in health and disease$20,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Derek Laver
Scheme Near Miss Grant
Role Lead
Funding Start 2007
Funding Finish 2007
GNo G0187200
Type Of Funding Internal
Category INTE
UON Y

3D Imaging Software/Work station$20,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Professor David Pow, Associate Professor Chris Dayas, Doctor Phil Jobling, Professor Derek Laver
Scheme Equipment Grant
Role Investigator
Funding Start 2007
Funding Finish 2007
GNo G0188026
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

(93) Hunter Medical Research Institute - Cardiovascular$3,551

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Derek Laver
Scheme Publication Performance Grant
Role Lead
Funding Start 2007
Funding Finish 2008
GNo G0187978
Type Of Funding Internal
Category INTE
UON Y

Biophysics Society, Baltimore Conference Centre, 3/3/2007 - 7/3/2007$2,500

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Derek Laver
Scheme Travel Grant
Role Lead
Funding Start 2007
Funding Finish 2007
GNo G0187324
Type Of Funding Internal
Category INTE
UON Y

20063 grants / $27,500

Mechanisms of action of w-3 fatty acids in control of atrial arrhythmias $16,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Professor Derek Laver, Professor Dirk Van Helden, Doctor Bonny Honen
Scheme Project Grant
Role Lead
Funding Start 2006
Funding Finish 2006
GNo G0186102
Type Of Funding Contract - Aust Non Government
Category 3AFC
UON Y

Regulation of calcium release channels by Ca2+ store load and phosphorylation$10,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Derek Laver
Scheme Near Miss Grant
Role Lead
Funding Start 2006
Funding Finish 2006
GNo G0186579
Type Of Funding Internal
Category INTE
UON Y

Biophysics Society 18-22 Feb 2006$1,500

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Derek Laver
Scheme Travel Grant
Role Lead
Funding Start 2006
Funding Finish 2006
GNo G0186562
Type Of Funding Internal
Category INTE
UON Y

20052 grants / $137,278

Intrinsic properties of the pore forming domain of the Ryanodine Receptor Calcium Channel$135,000

Funding body: ARC (Australian Research Council)

Funding body ARC (Australian Research Council)
Project Team Professor Derek Laver
Scheme Discovery Projects
Role Lead
Funding Start 2005
Funding Finish 2007
GNo G0185058
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

2005 Annual meeting of the Biophysical Society, 12-16 Feb 2005, USA$2,278

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Derek Laver
Scheme Travel Grant
Role Lead
Funding Start 2005
Funding Finish 2005
GNo G0185126
Type Of Funding Internal
Category INTE
UON Y

20041 grants / $12,903

Regulation of normal and diseased cardiac Ca+ channels$12,903

Funding body: NIH National Institutes of Health

Funding body NIH National Institutes of Health
Project Team Professor Derek Laver
Scheme Collaborative NIH Research Grant
Role Lead
Funding Start 2004
Funding Finish 2004
GNo G0185411
Type Of Funding Not Known
Category UNKN
UON Y

20034 grants / $190,500

Aberrant behaviour of cardiac calcium release channels induced by ryanodine receptor peptide probes$160,000

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Professor Derek Laver
Scheme Project Grant
Role Lead
Funding Start 2003
Funding Finish 2005
GNo G0183037
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

Mechanisms of action of omega-3 fatty acids in reduction of hypertension.$17,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Professor Derek Laver, Professor Dirk Van Helden
Scheme Research Grant
Role Lead
Funding Start 2003
Funding Finish 2003
GNo G0182641
Type Of Funding Contract - Aust Non Government
Category 3AFC
UON Y

C. elegans as an expression system for proteins that govern calcium release from internal stores.$11,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Derek Laver
Scheme Project Grant
Role Lead
Funding Start 2003
Funding Finish 2003
GNo G0182453
Type Of Funding Internal
Category INTE
UON Y

Gordon Conference on Muscle Contraction, New London, NH, USA 8 - 13 June, 2003$2,500

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Derek Laver
Scheme Travel Grant
Role Lead
Funding Start 2003
Funding Finish 2003
GNo G0182761
Type Of Funding Internal
Category INTE
UON Y

20024 grants / $523,961

Mechanisms governing regulation of ryanodine receptors function.$292,000

Funding body: ARC (Australian Research Council)

Funding body ARC (Australian Research Council)
Project Team Professor Derek Laver
Scheme Australian Senior Research Fellowship
Role Lead
Funding Start 2002
Funding Finish 2005
GNo G0181740
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

Mechanisms governing regulation of ryanodine receptors function.$110,861

Funding body: ARC (Australian Research Council)

Funding body ARC (Australian Research Council)
Project Team Professor Derek Laver
Scheme Large Grant
Role Lead
Funding Start 2002
Funding Finish 2003
GNo G0181739
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

Role of calcium stores and phosphate channells in muscular fatigue.$107,100

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Professor Derek Laver
Scheme Project Grant
Role Lead
Funding Start 2002
Funding Finish 2004
GNo G0181815
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

Dynamic Regulation Mechanisms of IP3-Receptor Calcium Release Channels$14,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Derek Laver
Scheme New Staff Grant
Role Lead
Funding Start 2002
Funding Finish 2002
GNo G0182022
Type Of Funding Internal
Category INTE
UON Y
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Research Supervision

Number of supervisions

Completed10
Current2

Total current UON EFTSL

PhD1.3

Current Supervision

Commenced Level of Study Research Title Program Supervisor Type
2016 PhD The Single Channel RyR Measurements and the Effects of Mutant CaM on Channel Function. PhD (Human Physiology), Faculty of Health and Medicine, The University of Newcastle Principal Supervisor
2015 PhD Mechanosensitivity of TRPC6 Channels and its Role in Mechanoelectric Feedback of the Heart PhD (Human Physiology), Faculty of Health and Medicine, The University of Newcastle Principal Supervisor

Past Supervision

Year Level of Study Research Title Program Supervisor Type
2016 PhD Effects of Calmodulin on Function of Cardiac and Skeletal Ryanodine Receptors PhD (Human Physiology), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2016 PhD In Vivo Investigations into the Effects of Pathological Conditions Including Diabetes on Lymphatic Function and Wound Healing PhD (Human Physiology), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2014 PhD Mechanisms of Cardiac Ryanodine Receptor Inhibition by Anti Arrhythmic Drugs PhD (Human Physiology), Faculty of Health and Medicine, The University of Newcastle Principal Supervisor
2014 PhD Regulation of Calcium Release Channels (RyR2) in Healthy and Failing Human Hearts PhD (Human Physiology), Faculty of Health and Medicine, The University of Newcastle Principal Supervisor
2013 PhD Regulation of Cardiac Calcium Release Channels During Acute Beta-Adrenergic Stimulation PhD (Human Physiology), Faculty of Health and Medicine, The University of Newcastle Principal Supervisor
2006 PhD Determinates of GABAA receptor single channel conductance Biol Sc Not Elsewhere Classifd, Australian National University Co-Supervisor
2004 Honours The effect of poly unstaturated fatty acids on Ca2+ sparks Biol Sc Not Elsewhere Classifd, University of Newcastle Co-Supervisor
2002 PhD A study of the effect of ryanodine receptor oxidation on its regulation by myoplasmic substances Biol Sc Not Elsewhere Classifd, Australian National University Co-Supervisor
2002 PhD The effects of protein-protein interactions on the functioning of ryanodine receptors Biol Sc Not Elsewhere Classifd, Australian National University Co-Supervisor
1999 PhD A study of desensitization in GABAA receptors Biol Sc Not Elsewhere Classifd, Australian National University Co-Supervisor
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News

Cardiology Riddle solved in 3D heartbeat

Cardiology riddle solved in 3D heartbeat

June 21, 2013

Using sophisticated computer modelling, a University of Newcastle researcher has helped find the missing piece to a 20-year cardiology puzzle – working out precisely how the heart regulates its beat.

Professor Derek Laver

Position

Professor
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine

Focus area

Human Physiology

Contact Details

Email derek.laver@newcastle.edu.au
Phone (02) 4921 8732
Fax (02) 4921 7406

Office

Room MS407
Building Medical Sciences
Location Callaghan
University Drive
Callaghan, NSW 2308
Australia
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