THE INWARD RECTIFICATION MECHANISM OF THE HERG CARDIAC POTASSIUM CHANNEL

A human genetic defect associated with 'long Q-T syndrome', an abnorma lity of cardiac rhythm involving the repolarization of the action pote ntial, was recently found to lie in the HERG gene, which codes for a p otassium channel(1). The HERG K+ channel is unusual in that it seems t o have the architectural plan of the depolarization-activated K+ chann el family (six putative transmembrane segments), yet it exhibits recti fication like that of the inward-rectifying K+ channels, a family with different molecular structure (two transmembrane segments)(2-4). We h ave studied HERG channels expressed in mammalian cells and find that t his inward rectification arises from a rapid and voltage-dependent ina ctivation process that reduces conductance at positive voltages. The i nactivation gating mechanism resembles that of C-type inactivation, of ten considered to be the 'slow inactivation' mechanism of other K+ cha nnels. The characteristics of this gating suggest a specific role for this channel in the normal suppression of arrhythmias.