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(Circulation. 2005;112:1376-1378.)
© 2005 American Heart Association, Inc.

Editorial

Protecting the Heart Against Arrhythmias: Potassium Current Physiology and Repolarization Reserve

Dan M. Roden, MD; Tao Yang, PhD

From the Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tenn.

Correspondence to Dan M. Roden, MD, Director, Oates Institute for Experimental Therapeutics, Vanderbilt University School of Medicine, 532 Medical Research Building I, Nashville, TN 37232. E-mail dan.roden@vanderbilt.edu

Key Words: Editorials • arrhythmia • ion channels • potassium • repolarization

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Hodgkin and Huxley’s classic experiments in the squid giant axon were the first to define a role for potassium efflux as a mechanism to return the membrane potential of an excitable cell to resting values.¹ They showed that depolarization was caused by a rapid influx of sodium into the squid giant axon, an event which then initiated movement of potassium from inside the axon to the exterior. The resulting repolarizing current, termed I_K, was identified decades later as a major contributor to repolarization in heart cells.² I_K appeared to not only drive normal repolarization but also respond to adrenergic activation. By the 1970s it was apparent that ß-adrenergic stimulation markedly increases inward calcium current in myocytes³; this would prolong the QT interval on exercise were it not for a "balancing" effect of I_K activation.⁴

See p 1384 and 1392

	Separating IK Into IKr and IKs in Heart

 
In the late 1980s, there was some enthusiasm for the concept that arrhythmias could be suppressed by drugs that selectively delay repolarization (ie, without exerting other electrophysiological effects such as sodium channel block). A number of potent QT-prolonging agents were developed; in fact, 2—dofetilide and ibutilide—have reached clinical use. Studies of the molecular basis of such selective action potential prolongation led to the key discovery by Michael Sanguinetti, then at Merck, that "I_K" in guinea pig myocytes actually represented 2 distinct currents: a small drug-sensitive current that activated rapidly (hence, termed I_Kr) and a large drug-resistant currrent that activated slowly, I_Ks.⁵ I_Kr block is now . . . [Full Text of this Article]

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