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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.
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Revised: Relationship between early and late events in the cardiac cycle as control points of pharmacological intervention
1/02/16 → 31/01/21
Termination of calcium-induced calcium release by induction decay: An emergent property of stochastic channel gating and molecular scale architectureLaver, D. R., Kong, H. T., Imtiaz, M. & Cannell, M. B., 2013, In: Journal of Molecular and Cellular Cardiology. 54, p. 98-100 2 p.
Research output: Contribution to journal › Article (Academic Journal) › peer-review56 Citations (Scopus)
Excitation-contraction coupling in human heart failure examined by action potential clamp in rat cardiac myocytesCooper, P. J., Soeller, C. & Cannell, MB., Dec 2010, In: Journal of Molecular and Cellular Cardiology. 49, p. 911 - 917 6 p.
Research output: Contribution to journal › Article (Academic Journal) › peer-review24 Citations (Scopus)
Organization of ryanodine receptors, transverse tubules, and sodium-calcium exchanger in rat myocytesJayasinghe, I. D., Cannell, MB. & Soeller, C., Nov 2009, In: Biophysical Journal. 97, p. 2664 - 2673 9 p.
Research output: Contribution to journal › Article (Academic Journal) › peer-review88 Citations (Scopus)
Mark B Cannell (Editor)Dec 2019 → …
Activity: Publication peer-review and editorial work types › Editorial activity