Mallotoxin is a novel human ether-a-go-go-related gene (hERG) potassium channel activator.

摘要: Human ether-a-go-go-related gene (hERG) encodes a rapidly activating delayed rectifier potassium channel that plays important roles in cardiac action potential repolarization. Although many drugs and compounds block hERG channels, activators of the have only recently been described. Three structurally diverse synthetic reported to activate channels by altering deactivation or inactivation unidentified mechanisms. Here, we describe novel, naturally occurring activator, mallotoxin (MTX). The effects MTX on were investigated using patch-clamp technique. increased both step tail currents with EC(50) values 0.34 0.52 microM, respectively. leftward shifted voltage dependence activation less depolarized voltages ( approximately 24 mV at 2.5 microM). In addition, time constants. did not change half-maximal channel, but it reduced slope voltage-dependent curve. All these factors contribute enhanced activity channels. During voltage-clamp protocol prerecorded potentials, microM total ions passed through 5-fold. conclusion, activates distinct mechanisms significantly higher potency than previously activators.