Assistant Professor
Ph.D. Biomedical Sciences, University of Leeds - 2001
Postdoctoral: University of British Columbia - 2004-2007
Phone: (778) 782-8514
Fax: (778) 782-3040
Email: thomas_claydon@sfu.ca
Molecular Cardiac Physiology Group
Available Positions: Postdoctoral Fellow & Graduate Students
Research overview:
Ion channels are proteins that form ion-selective pores within cell membranes. In the heart, ion channels establish and maintain normal cardiac rate and rhythm, and changes in their function due to genetic or environmental causes can lead to life-threatening alterations of the cardiac rhythm. Despite such a critical role, the dynamic molecular mechanisms underlying ion channel function and how these are modulated by cardiovascular disease are unclear. In our research, we use fluorescence-based electrophysiology approaches to study ion channel behaviour. These cutting-edge techniques provide a novel and innovative tool to study the relationship between ion channel dynamic structure and its function. They allow us to directly observe changes in channel protein structure that underlie normal function and to visualize the effects of polymorphisms and environmental changes that are associated with cardiovascular disease. This gives us a new and powerful way to study ion channel biophysics and physiology.
Current Research Projects:
1. Cardiac ion channel structural dynamics: Our work focuses on cardiac ion channels, such as sodium channel and potassium channels, including the human ether-a-go-go-related gene (hERG) potassium channel, which play key roles in cardiac repolarization and the termination of the action potential. Our goal is to use fluorescence-based techniques to understand the structural determinants of the unique gating processes in these channels and how they are modulated by polymorphisms and changes in the cellular environment that are associated with cardiovascular disease. These techniques include voltage clamp fluorimetry (VCF), fluorescence resonance energy transfer (FRET) and fluorescence lifetime microscopy (FLM).
2. Regulation of cardiac ion channel function by acidosis: Acidosis is a consequence of myocardial ischemia and is associated with arrhythmia and sudden death. Acidosis suppresses potassium channel currents and this may contribute to arrhythmogensis. We are working on understanding the molecular mechanisms by which protons inhibit channel function. Using fluorescence-based electrophysiology applications we have recently demonstrated that acidic pH inactivates channels that are open, but also acts directly on resting closed channels preventing them from opening at all. This has profound effects on channel function during the cardiac action potential.
Selected Recent Publications:
T.W.Claydon and D.Fedida (2007). Voltage clamp fluorimetry studies of mammalian voltage-gated K+ channel gating. Biochemical Society Transactions 35, 1080-1082.
T.W.Claydon, M.Vaid, S.Rezazadeh, S.Kehl, D.Fedida (2007). A direct demonstration of closed-state inactivation of K+ channels at low pH. Journal of General Physiology 129, 437-455.
T.W.Claydon, M.Vaid, S.Rezazadeh, S.Kehl, D.Fedida (2007). 4-aminopyridine prevents the conformational changes in Shaker channels associated with P/C-type inactivation. Journal of Pharmacology and Experimental Therapeutics 320, 162-172.
T.W.Claydon, M.R.Boyett, A.Sivaprasadarao, C.H.Orchard (2002). Two extracellular pore residues mediate acidosis-induced enhancement of C-type inactivation of the K+ Kv1.4. American Journal of Physiology 283, C1114-1121.
T.W.Claydon, M.R.Boyett, A.Sivaprasadarao, K.Ishii, J.M.Owen, H.A.O’Beirne, R.Leach, K.Komukai, C.H.Orchard (2000). Inhibition of the K+ channel Kv1.4 by acidosis: protonation of an extracellular histidine slows the recovery from N-type inactivation. Journal of Physiology 526, 253-264.
For a full pubmed listing of publications, visit: PubMed