Research
Cardiac electrophysiology
Our recent work has focused on the consequences of abnormal Ca2+ homeostasis for cardiac function. We have shown that increased diastolic Ca2+ produces a significant decrease in action potential conduction velocity in both atria (1) and ventricles (2), and that there is a significant correlation between slowed conduction and arrhythmogenicity. These findings directly suggest novel strategies for research, diagnosis and treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT) (see e.g. here), as described in two recent editorials on our papers (here and here).
Skeletal muscle electrophysiology
Our work with skeletal muscle forms two broad streams. The first aims to feed findings into my group's cardiac research, while the second is aimed at understanding skeletal muscle electrophysiology with direct relevance to human diseases. The recent focus of the first stream has been on understanding the determinants of conduction velocity in muscle. We have been able to show precisely how conduction velocity is determined and how it is influenced by changes in structure and electrophysiology in health and disease (e.g. here and here). This has informed our work exploring the mechanisms that link abnormal cardiac Ca2+ homeostasis with slowed conduction. Our work in the second stream has recently provided insight into the phenotypic variation in myotonia congenita.
Collaborators
Prof Chris Huang, Department of Physiology, Development and Neuroscience, University of Cambridge
Dr Folma Buss, Department of Clinical Biochemistry, Addenbrooke’s Hospital, University of Cambridge
Dr Andrew Grace, Department of Biochemistry, University of Cambridge
Assoc Prof Thomas Pedersen, Institute of Physiology and Biophysics, University of Aarhus, Denmark
Prof Aiqun Ma, Department of Cardiovascular Medicine, Xi'an Jiaotong University, China
Prof Ron Horgan, Department of Applied Mathematics and Theoretical Physics, University of Cambridge
Dr Ming Lee, Institute of Cardiovascular Science, University of Manchester
Dr Yanmin Zhang, Xi'an Jiaotong University, China
Publications
Salvage SC, King JH, Chandrasekharan KH, Jafferji DIG, Guzadhur L, Matthews HR, Huang CL-H, Fraser JA, (2015), Flecainide exerts paradoxical effects on sodium currents and atrial arrhythmia in murine RyR2-P2328S hearts, Acta Physiologica, 214(3), pp.361–375
Sim J, Fraser JA, (2014), The determinants of transverse tubular volume in resting skeletal muscle, The Journal of physiology, 592(Pt 24), pp.5477–92
Lu L, Fraser JA (2014), Functional consequences of NKCC2 splice isoforms: insights from a Xenopus oocyte model, American journal of physiology, Renal physiology, 306(7), pp.F710–20
Zhang Y, Wu J, Jeevaratnam K, King JH, Guzadhur L, Ren X, Grace AA, Lei M, Huang CL-H, Fraser JA, (2013), Conduction slowing contributes to spontaneous ventricular arrhythmias in intrinsically active murine RyR2-P2328S hearts, Journal of cardiovascular electrophysiology, 24(2), pp.210–8
King JH, Zhang Y, Lei M, Grace AA, Huang CLH, Fraser, JA, (2013), Atrial arrhythmia, triggering events and conduction abnormalities in isolated murine RyR2-P2328S hearts, Acta Physiologica, 207(2), pp.308–323
King JH, Huang CLH, Fraser JA, (2013), Determinants of myocardial conduction velocity: Implications for arrhythmogenesis, Frontiers in Physiology, 4 JUN, p.154
King JH, Wickramarachchi C, Kua K, Du Y, Jeevaratnam K, Matthews HR, Grace AA, Huang CLH, Fraser JA, (2013), Loss of Nav1.5 expression and function in murine atria containing the RyR2-P2328S gain-of-function mutation, Cardiovascular Research, 99(4), pp.751–759
King JH, Zhang Y, Huang CL-H, Fraser JA, (2012), The Relationship Between Conduction Velocity and Atrial Arrhythmogenicity under Conditions of Altered Ca2+ Homeostasis in RyR2-P2328S Murine Hearts, Biophysical Journal, 102(3), p.671a
Pedersen TH, Huang CL-H, Fraser JA, (2011), An analysis of the relationships between subthreshold electrical properties and excitability in skeletal muscle, The Journal of general physiology, 138(1), pp.73–93
Fraser JA, Huang CL-H, Pedersen TH, (2011), Relationships between resting conductances, excitability, and t-system ionic homeostasis in skeletal muscle, The Journal of general physiology, 138(1), pp.95–116
Fraser JA, Huang CL-H, (2007), Quantitative techniques for steady-state calculation and dynamic integrated modelling of membrane potential and intracellular ion concentrations, Progress in biophysics and molecular biology, 94(3), pp.336–72
Fraser JA, Huang CL-H, (2004), A quantitative analysis of cell volume and resting potential determination and regulation in excitable cells, The Journal of physiology, 559(Pt 2), pp.459–78
Teaching and Supervisions
I give the following lectures: MVST 1A: Heart and Circulation (5 lectures), MVST 1A: Renal Physiology and Body Fluid Homeostasis (6 lectures), NST 1B Physiology: the Mammalian Circulation (5 lectures), NST II Physiology: Mathematical Modelling in Physiology (2 lectures)
I also teach the following practical classes for NST Part II: Cellular modelling (2 afternoons), Microelectrodes I (2.5 days), Microelectrodes II (2.5 days), Loose Patch Clamp (2 days)
