Fig. 1. hERG channel gating. (A) At negative membrane potentials hERG channels are in closed state. The voltage sensor domain (+++) is in the down conformation and the cytoplasmic part of the S5/S6 helix bundle prevents the flow of ions (*). (B) Upon depolarization the channels slowly activate: the voltage sensor domain transitions upwards within the membrane. Via the S4S5 linker this motion is transferred onto the cytoplasmic end of the helix bundle, and the pore allows potassium ions to flow. (C) The channels rapidly undergo inactivation, which is characterized by a collapse of the selectivity filter (*), preventing any further flow of potassium ions.