Referenced in: none

Automatically associated channels: Kv11.1 , Kv7.1

Title: I(Kr): the hERG channel.

Authors: G N Tseng

Journal, date & volume: J. Mol. Cell. Cardiol., 2001 May , 33, 835-49

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11343409

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 understanding of I(Kr)/hERG, particularly in the areas of roles of different (& agr; and & bgr;) subunits in native I(Kr)function, alterations in I(Kr)function in diseased hearts, and the 3-dimensional structure of the I(Kr)/hERG pore based on homology modeling using the KcsA model, will help us better define the role of I(Kr)in arrhythmias and design therapeutic agents that can increase I(Kr)and are useful for LQT syndrome.