Professor Terence J Campbell

Professor Terence J Campbell, MD PhD FRACP FACC Deputy Director, Victor Chang Cardiac Research Institute Laboratory Head, Molecular Cardiology and Biophysics Division Professor of Medicine, University of New South Wales Head, University Department of Medicine, St Vincent's Hospital Telephone: +61-2-8382 2352 Fax: +61-2-8382 2794 Email: t.campbell@unsw.edu.au

Research Focus:
Our current research programs involve: HERG K+ channels; Molecular basis of voltage sensing; and Two pore K+ channels;

Arrhythmias represent the end product of abnormal ion-channel function, whether that be due to genetic mutations, inhibition by drugs, modulation by metabolic insults (e.g. during myocardial ischaemia), or altered levels or spatial patterns of expression such as occurs in heart failure. Of the many channels that contribute to cardiac electrical activity, potassium ion channels encoded by the Human ether-a-go-go-related gene (HERG) have been of particular interest because malfunction of HERG K+ channels, due to inherited mutations or inhibition by drugs can cause long QT syndrome. Furthermore, they have very unusual gating kinetics. Our previous studies, as well as those of others suggest that the key features of HERG K+ channel gating that contribute to its anti-arrhythmic properties are rapid voltage dependent inactivation/recovery from inactivation and slow activation/deactivation.

We have two main projects going on in the laboratory directed at understanding the unusual kinetics of HERG: 1) Investigating the nature of the voltage sensor in HERG and 2) Studying the structural basis of rapid inactivation in HERG. We are using a range of electrophysiological techniques as well as site-directed mutagenesis, scorpion toxins and NMR structural studies to address these problems.

The newest project in the lab is directed at understanding the structure and function of two pore K+ channels. These channels are commonly referred to as "leak channels", however, the activity of these channels is tightly regulated and they are likely to contribute to a range of functions in the heart including setting the resting membrane potential.

Co-Investigators:
Adam Hill, PhD
Ken Wyse, BSc
Stefan Mann, PhD
Tadeusz Marciniec
Mark Perrin
Mark Hunter, BSc
David Wang

Collaborators:
Paul Alewood, PhD; Institute for Molecular Biosciences, Brisbane, Australia
Robert Graham, FAA, MD, FRACP, FACP, FAHA; VCCRI, Sydney, Australia
Christopher Huang, MBBChir, DSc; University of Cambridge, Cambridge, UK
Philip Kuchel, PhD; University of Sydney, Sydney, Australia
Martyn Mahaut-Smith, PhD; University of Cambridge, Cambridge, UK
Tony Varghese, PhD; University of Minnesota, MN, USA

Selected Publications:
Torres AM, Bansal PS, Sunde M, Clarke CE, Bursill JA, Smith DJ, Bauskin A, Breit SN, Campbell TJ, Alewood PF, Kuchel PW, Vandenberg JI. Structure of the HERG K+ channel S5P extracellular linker: Role of an amphipathic alpha-helix in c-type inactivation. J Biol Chem 2003; 278:42136-42148

Subbiah RN, Clarke CE, Smith DJ, Zhao J, Campbell TJ, Vandenberg JI. Molecular basis of slow activation of the human ether-a-go-go related gene (HERG) K+ channel. J Physiol 2004; 558:417-431

Vandenberg JI, Torres AM, Campbell TJ, Kuchel PW. The HERG K+ channel: Progress in understanding the molecular basis of its unusual gating kinetics. Europ Biophys J 2004; 33: 89-97

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