Human ether-a-go-go-related (HERG) gene and ATP-sensitive potassium channels as targets for adverse drug effects

Pharmacology & Therapeutics
Bernd J Zünkler

Abstract

Torsades de pointes (TdP) arrhythmia is a potentially fatal form of ventricular arrhythmia that occurs under conditions where cardiac repolarization is delayed (as indicated by prolonged QT intervals from electrocardiographic recordings). A likely mechanism for QT interval prolongation and TdP arrhythmias is blockade of the rapid component of the cardiac delayed rectifier K+ current (IKr), which is encoded by human ether-a-go-go-related gene (HERG). Over 100 non-cardiovascular drugs have the potential to induce QT interval prolongations in the electrocardiogram (ECG) or TdP arrhythmias. The binding site of most HERG channel blockers is located inside the central cavity of the channel. An evaluation of possible effects on HERG channels during the development of novel drugs is recommended by international guidelines. During cardiac ischaemia activation of ATP-sensitive K+ (KATP) channels contributes to action potential (AP) shortening which is either cardiotoxic by inducing re-entrant ventricular arrhythmias or cardioprotective by inducing energy-sparing effects or ischaemic preconditioning (IPC). KATP channels are formed by an inward-rectifier K+ channel (Kir6.0) and a sulfonylurea receptor (SUR) subunit: Kir6.2 and SUR2A in car...Continue Reading

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Citations

May 9, 2009·Naunyn-Schmiedeberg's Archives of Pharmacology·Dong-fang GuBao-feng Yang
Apr 17, 2008·The Journal of Membrane Biology·Sonja ClaassenBernd J Zünkler
May 15, 2010·Cardiovascular Toxicology·Bernd J Zünkler, Maria Wos-Maganga
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May 6, 2009·Clinical and Experimental Pharmacology & Physiology·Xiu-Lan Sun, Gang Hu
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Mar 25, 2021·Clinical Pharmacology in Drug Development·Jin-Woo ParkJi-Young Park
Dec 17, 2021·Journal of the American Heart Association·Ohad OrenDeepak L Bhatt

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