Professor of Cardiac Electrophysiology
Professor Tinker undertook medical training in Oxford and London and qualified in the UK as a physician becoming a Member of the Royal College of Physicians. He was then awarded an MRC Clinical Training Fellowship to work with Alan Williams at the National Heart and Lung Institute on how calcium is released from internal stores to cause cardiac contraction. After obtaining his PhD, he pursued postdoctoral studies at UCSF with Lily Jan as a Wellcome Trust Intermediate Clinical Fellow. The Jan group were the pioneers in cloning the first potassium channels and whilst there he investigated the basic molecular properties of the inward rectifier family. He returned to the UK to establish his own laboratory at UCL with the award of a Wellcome Trust Senior Fellowship in Clinical Science. He has continued his interests in the molecular properties and regulation of potassium channels in the cardiovascular system (and other tissues) and has published productively in internationally respected journals over this period. He obtained a Chair in Molecular Medicine at UCL in 2004 and was made a Fellow of the Academy of Medical Sciences for his achievements in this field in 2008. He is currently supported by programme grants from the British Heart Foundation (first awarded in 2005 and renewed in 2011) and the Wellcome Trust. He has just taken up the Chair of Cardiac Electrophysiology at the new £25 million William Harvey Heart Centre at Queen Mary University of London.
Summary of Research
We are interested in what role potassium channels and cell signalling proteins play in cardiac (patho)physiology. The question is how these might act to reinforce normal heart rhythm or act as substrates for cardiac arrhythmia. We have specific interests in a range of potassium channels and heterotrimeric G-protein signalling in the heart and blood vessels. Technically we are using unique strains of genetically modified mice and we combine this with murine phenotyping capabilities including single-cell electrophysiology and imaging of cardiac myocytes (ventricular, atrial and SA nodal), telemetry and electrophysiology studies. In addition, we also have an established track record in molecular and cellular studies in these areas and are still performing such work. I have several very distinctive research strands being pursued in my laboratory with a focus on ATP-sensitive K+ channels, G-protein gated inwardly rectifying K+ channels and cardiac channelopathies.
Induction of ventricular tachycardia
Measurement of VERP in a mouse
For a full list of publist publications click here
THOMAS, A.M., HARMER, S.C., KHAMBRA, T. & TINKER, A. (2011). Characterisation of a binding site for anionic phospholipids on KCNQ1. Journal of Biological Chemistry. 286, 2088-100.
SCHWARZER, S., NOBLES, M. & TINKER, A. (2010). Do caveolae have a role in the fidelity and dynamics of receptor activation of G-protein gated inwardly rectifying potassium channels? Journal of Biological Chemistry 285, 27817-26.
ZUBERI, Z., NOBLES, M., SEBASTIAN, S., DYSON, A., SHIANG, Y., BRECKENRIDGE, R., BIRNBAUMER, L. & TINKER, A. (2010). Absence of the inhibitory G-protein, G?i2, predisposes to ventricular cardiac arrhythmia. Circulation: Arrhythmia and Electrophysiology 3, 391-400.
CAMPANELLA, M., CASSWELL, E., CHONG, S., FARAH, Z., WIECKOWSKI, M.R., ABRAMOV, A.R., TINKER, A. & DUCHEN, M.R. (2008). Regulation of mitochondrial structure and function by IF1, the endogenous inhibitor of the mitochondrial ATPase. Cell Metabolism 8, 13-25.
NOBLES, M., BENIANS, A. & TINKER, A. (2005). Heterotrimeric G proteins precouple with G-protein coupled receptors in living cells. Proceedings of the National Academy of Sciences (USA) 102, 18706-11.
WILSON, A.J., QUINN, K.V., GRAVES, F.M., BITNER-GLINDZICZ, M. & TINKER, A. (2005).Abnormal KCNQ1 trafficking influences disease pathogenesis in hereditary long QT syndromes (LQT1). Cardiovascular Research 67, 476-86.
QUINN, K., GIBLIN, J., & TINKER, A. (2004) A multi-site phosphorylation mechanism for protein kinase A activation of the smooth muscle ATP-sensitive K+ channel. Circulation Research 94, 1359-1366.
QUINN, K., CUI, Y., GIBLIN, J., CLAPP, L.H. & TINKER, A. (2003) Do anionic phospholipids serve as cofactors or second messengers for the regulation of activity of cloned ATP-sensitive K+ channels? Circulation Research 93, 646-655.
LEANEY, J.L. & TINKER, A. (2000). The role of members of the pertussis toxin-sensitive family of G proteins in coupling receptors to the activation of the G protein-gated inwardly rectifying potassium channel. Proceedings of the National Academy of Sciences (USA) 97, 5651-5656 (submitted via track II).
TINKER, A, JAN Y.N. & JAN L.Y. (1996). Regions responsible for the assembly of inwardly rectifying potassium channels. Cell 87, 857-868.