Calcium-dependent Mechanisms Underlying Beat-to-Beat Variability of Repolarization in Cardiac Hypertrophic remodeling.

The major function of the heart is to continually pump blood through the circulatory system of the entire body to provide nutrients and oxygen whilst removing waste, hence careful regulation is essential. The pump function is driven by electrical signals (action potentials), which are caused as a result of opening and closing of ion channels across the membrane of cardiac myocytes. In mammalian ventricular myocytes the action potential consists of a phase where calcium ions enter through specific ion channels subsequently causing a global and transient increase in calcium in the cell that is essential for the twitch contraction. This increase is not the same in the whole cell and can be quite high in microdomains near the cell membrane where the ion channels reside that are responsible for the action potential. Under normal circumstance there is a low variability in action potential duration on a beat by beat basis, however in heart disease such as caused by a heart attack, this variability increases and this is thought to contribute to heart rhythm disturbances. We propose that alterations in the microdomains of calcium near the membrane may be the driver for variability in action potential duration under those circumstances. The aim of this project is to use electrophysiological techniques in myocytes to investigate the relationship between microdomain calcium, ionic channels under control of this calcium, and the risk for rhythm disturbances.