My Research

My research focuses mainly on the heart, in particular the mechanisms by which the heart cells (cardiomyocytes; below) regulate calcium in health and disease.

Isolated rat cardiomyocytes

Cardiomyocyte contraction is strictly dependent on calcium ions. During diastole (that is the resting state), calcium concentrations within the cell is very low. During systole (the contracting state), the electrical signals that spreads through the heart causes calcium to be released from storage compartments within the cardiomyocyte, called the sarcoplasmic reticulum (SR). This then leads to a massive increase in calcium concentration within the cell. The calcium then binds to the contractile filaments and leads to contraction. The process of converting the electrical stimulus to mechanical contraction is called Excitation-Contraction Coupling (EC Coupling). Click the button below to see an animation of EC Coupling at work.

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For the heart to function properly, it is important that calcium within the cardiomyocyte is tightly controlled at several different levels. First of all, calcium release from the SR should only occur when there is a signal, otherwise arrhythmias (abnormal heart rhythms) may occur. Second, since the calcium within the SR determines the contractile force, during diastole the SR has to refill with calcium, ready for the next contractile cycle. Some calcium also enters the cardiomyocyte from outside during systole and this calcium has to be extruded from the cardiomyocyte, to maintain a constant calcium concentration within the cardiomyocyte.  Underfilling or overfilling of the SR has dire consequences for the heart as a whole. For instance, calcium overload in the SR can lead to spontaneous calcium release, that is, in the absence of any electrical stimulations. During many diseased states, this fine regulation is lost and abnormal calcium handling is the cause of many cardiomyopathies (heart cell diseases).

So how are these studied in a laboratory? We can look at changes in calcium concentrations within the cardiomyocyte using fluorescent probes. Put simply, a fluorescent molecule sensitive only to calcium is loaded into the cardiomyocytes. When calcium binds, it fluoresces and this fluorescence is recorded. This is a very powerful tool to look at how calcium release is controlled, and also to quantify calcium release.

We can also look at the currents across the surface membrane of the cardiomyocyte.

COMING SOON!