Department of Physiology, Anatomy & Genetics


The Cardiac Mechano-Electric Feedback Group
(last revised on 04 November 2009)

Peter Kohl, MD, PhD, BHF SRF e-mail
Reader in Cardiac Physiology, University of Oxford
Adjunct Associate Professor, University of Maryland Biotechnology Institute
Tutor in Biomedical Sciences, Balliol College Oxford

Team Members:

Current Students:

Research Visitors:

Past Research Staff:

Topical Links:

Research:

Cardiac electrical and mechanical activity are closely interrelated. However, this is not a unidirectional process where electrical excitation controls cardiac contraction. There are powerful feedback mechanisms from the heart’s mechanical environment to its electrical activity. This Mechano-Electric Feedback (MEF) is the subject of investigations in this lab, which was founded in 1998, initially with the financial help of the BHF and the Royal Society, and now enjoying generous additional support from the BBSRC and the MRC.

MEF influences pacemaker rate, causes diastolic depolarisation, and affects action potential repolarisation. It contributes to the positive chronotropic response of the heart to stretch, transient-stretch induced ectopic excitation (including sudden cardiac death after moderate precordial impact - Commotio cordis) and arrhythmogenesis in pressure or volume overloaded hearts. On the other hand, if used appropriately, pre-cordial impact can be a highly efficient means of mechanical pacemaking and cardioversion. Mechanisms of cardiac MEF include stretch-activation of ion channels, mechanical modulation of Ca2+ handling, and interaction with other mechano-sensitive cells in the heart (not restricted to myocytes only). We study these mechanisms in isolated cardiac cells, cell pairs, cultures and Langendorff preparations. Methods include the single and double whole cell patch clamp techniques, fluorescence and confocal microscopy, and optical mapping. Interventions involve axial stretch of isolated cells, swelling, local cell membrane deformation, stretch applied to deformable cell-culture substrates, and controlled external stimulation of the intact heart. Having originally developed as part of Professor Denis Noble’s BHF Chair for Cardiovascular Physiology, we make extensive use of mathematical modelling for data interpretation, hypothesis formation, and design of experimental protocols.

The members of our group interact closely; an open environment and regular ‘coffee mornings’ help to ensure that everyone is kept up-to-date about the progress (or lack thereof :) in various projects. It also means that all team members are directly involved in research & administrative decision-making. We have close links to experimental and modelling teams in Auckland (A1, A2), Boston, Ekaterinburg, Heidelberg, Johns Hopkins, and San Diego, and contribute to several European Initiatives in Physiome-style research and development, such as BioSim, STEP, normaCOR, and the network of excellence for research directed at the Virtual Physiological Human.

Lecture Handouts:

FHS MVR Lecture on Mechanical Modulation of Heart Rate & Rhythm (22/10-09 5 PM), FHS MVR Lecture on Cellular Mechanisms of Cardiac MEF (22/10-09 4 PM), FHS MVR Lecture on Frank-Starling Response (27/10-09 5 PM).

Publications:

Perform PubMed search for Peter Kohl (excludes Journals such as Philosophical Transactions of the Royal Society A pre-August 2002, IEEE JOE or Chaos, Solitons & Fractals).