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Professor Mark Cannell

Professor Mark Cannell

Professor Mark Cannell
BSc(U.C.Lond.), PhD(U.C.Lond.), FRSNZ

Chair in Cardiac Cell Biology

Area of research

Computing and seeing a new solution to problems in the heart

Office DW2b
Biomedical Sciences Building,
University Walk, Bristol BS8 1TD
(See a map)

+44 (0) 117 331 1894

Summary

The bulk of my research has focussed on Ca signalling in cardiac cells, but I have also developed experimental and computational methods that are widely used in other biomedical research. I am probably best known for the discovery of Ca sparks, which are fundamental to thinking about (cardiac) Ca signalling. In subsequent work we described how the stochastic nature of Ca spark production and ‘local control theories’ can explain the voltage- and time-dependence of the Ca transient (which I first measured in 1987 after developing real time fluorescent Ca measurement in single cells in 1985).

By measuring Ca in single cells under voltage clamp, I also showed that Na-Ca exchange is the primary Ca extrusion system in ventricular muscle in 1990 (refuting the prevailing dogma that resting Ca was regulated by Ca ATPase).

We eventually developed a formalism for measuring EC coupling ‘gain’ based on Ca spark measurements and this was used to show a defect in microscopic EC coupling in heart failure. I suggested that this might arise from a reduction in co-localization between L-type Ca channels and sarcoplasmic reticulum Ca release channels, an idea that is steadily gaining importance with subsequent work showing disease-induced changes in the sub-cellular topology of the t-system in animal models and in human heart failure.

While stochastic Ca spark recruitment can explain the voltage- and time-dependence of the Ca transient, the key problem of Ca release termination has resisted our understanding for more than 20 years. We have recently proposed a new mechanism called ‘induction decay’ which provides a robust explanation for the termination of cardiac Ca release (Laver et al., (2013 J. Mol. Cell Cardiol. 54: 98–100). Therefore, in principle, the cellular basis of cardiac excitation-contraction coupling – from the initiation of Ca release to its termination – is now more clearly understood as a direct result of the research work I have enjoyed doing with many collaborators over the past ~30 years. With abundant evidence that defects in EC coupling and Ca cycling are major contributors to heart failure, the medical relevance of this basic science research is, I think, clear.

I also use detailed mathematical models to test hypotheses and enjoy developing new techniques and instruments.

Activities / Findings

My recent work has focussed in 4 main areas:

1) To clarify how Ca release from the intracellular Ca store is regulated

2) To improve methods for measuring local Ca signalling in cells -especially cardiac mycoytes

3) To apply high resolution imaging to clarifying how proteins are organized in the cardiac cell and how this orgnization affects function.

4) to try to undertsand how modufying electrical signalling can be exploited to improve contractility of the failing heart while also reducing the risk of sudden death.

Keywords

  • Calcium imaging
  • Heart muscle
  • Muscle function

Selected publications

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Recent publications

View complete publications list in the University of Bristol publications system

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