I(Kr): the hERG channel

Journal of Molecular and Cellular Cardiology
G N Tseng

Abstract

G.-N. Tseng. I(Kr): The hERG Channel. Journal of Molecular and Cellular Cardiology (2001) 33, 835-849. The rapid delayed rectifier (I(Kr)) channel is important for cardiac action potential repolarization. Suppressing I(Kr)function, due to either genetic defects in its pore-forming subunit (hERG) or adverse drug effects, can lead to long-QT (LQT) syndrome that carries increased risk of life-threatening arrhythmias. The implication of I(Kr)in cardiac arrhythmias and in anti-arrhythmic/pro-arrhythmic actions of drugs has driven intensive research interests in its structure-function relationship, the linkage between LQT-associated mutations and changes in channel function, and the mechanism of drug actions. This review will cover the following topics: (1) heterogeneous contribution of I(Kr)to action potential repolarization in the heart, (2) structure-function relationship of I(Kr)/hERG channels, (3) role of regulatory & bgr; subunits in I(Kr)/hERG channel function, (4) structural basis for the unique pharmacological properties of I(Kr)/hERG channels, and (5) I(Kr)/hERG channel modulation by changes in cellular milieu under physiological and pathological conditions of the heart. It is anticipated that further advances in our unders...Continue Reading

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