Examining the effects of activator compounds on hERG cardiac potassium channel protective currents conducted in response to premature stimulations

The human ether-a-go-go-related gene (hERG) encodes the rapid delayed rectifier cardiac potassium channel. Vital for repolarization of the myocardium and termination of the cardiac action potential, loss of function in hERG K+ channels can result in Long QT Syndrome Type II (LQTS2). Additionally, hERG channels have been shown to mediate robust repolarizing currents in response to premature depolarizations, reflective of channels remaining in the open state into the refractory period. Thought to be protective against afterdepolarizations, loss of function in this regard may leave individuals susceptible to arrhythmia. Recently, several small molecule activators of hERG have been discovered. The effects of these compounds on the protective currents mediated by hERG channels have yet to be studied. The work presented in this thesis examines the effects of both Type I and II hERG channel activators on protective currents mediated by hERG channels, in the context of an inherited mutation.