The inward rectification mechanism of the HERG cardiac potassium channel

Abstract

A HUMAN genetic defect associated with 'long Q–T syndrome', an abnormality of cardiac rhythm involving the repolarization of the action potential, was recently found to lie in the HERG gene, which codes for a potassium channel¹. The HERG K⁺ channel is unusual in that it seems to have the architectural plan of the depolarization-activated K⁺ channel family (six putative trans-membrane segments), yet it exhibits rectification like that of the inward-rectifying K⁺ channels, a family with different molecular structure (two transmembrane segments)^2–4. We have studied HERG channels expressed in mammalian cells and find that this inward rectification arises from a rapid and voltage-dependent inactivation process that reduces conductance at positive voltages. The inactivation gating mechanism resembles that of C-type inactivation, often considered to be the Slow inactivation' mechanism of other K⁺ channels. The characteristics of this gating suggest a specific role for this channel in the normal suppression of arrhythmias.