Computational Study of SCN5A L812Q Gene Mutation in Epicardial Cells

A simulation and analysis of gene mutation in sodium ion channel found in the epicardial cell is discussed. Effect of loss of function mutation on SCN5A gene due to L812Q mutant in the DII-S4 transmembrane region of the sodium channel protein is studied considering the steady state activation and inactivation, time constants, ionic currents and action potential of the epicardial cell. In general SCN5A mutation characterizes Brugada Syndrome and L812Q is a de novo mutation. The human ventricular action potential model by Ten Tusscher is modified to incorporate the changes contributed by L812Q mutant in the cells. Results show that this mutation causes reduced amplitude of inward sodium current (I_{N}a) due to certain modifications in channel gating dynamics such as delayed activation, enhanced inactivation and slowed recovery from inactivation in the epicardial cell. This decrease in I_{N}a affect the depolarization phase (Phase0) of cardiac action potential that leads to reduction in the spike amplitude.