This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sanguinetti, M. C. Search for Related Content PubMed PubMed Citation Articles by Sanguinetti, M. C. Related Collections Cell signalling/signal transduction Hypertrophy Ion channels/membrane transport

(Circulation Research. 2002;90:497.)
© 2002 American Heart Association, Inc.

Editorials

Reduced Transient Outward K⁺ Current and Cardiac Hypertrophy

Causal Relationship or Epiphenomenon?

Michael C. Sanguinetti

From the Department of Physiology, University of Utah, Salt Lake City, Utah.

Correspondence to Michael C. Sanguinetti, Eccles Institute of Human Genetics, 15 N 2030 E, Room 4220, University of Utah, Salt Lake City, UT 84112. E-mail michael.sanguinetti@hmbg.utah.edu

Key Words: potassium channels • heart failure • calcineurin

Action potentials coordinate contraction and relaxation of the heart. The long plateau phase of the action potential ensures sufficient Ca²⁺ entry into the cytoplasm via L-type Ca²⁺ channels to invoke Ca²⁺-induced Ca²⁺ release from the sarcoplasmic reticulum and activation of the contractile filaments. Action potentials are initiated by opening of voltage-gated Na⁺ channels that in turn rapidly depolarize the membrane and open voltage-gated Ca²⁺ and K⁺ channels. Some K⁺ channels activate immediately in response to depolarization, then inactivate within tens of milliseconds later, and mediate a current called the transient outward K⁺ current (I_to). In many mammalian hearts, including human, I_to is responsible for the initial rapid phase of action potential repolarization, discernible as a notch preceding the plateau phase, but has little role in terminal repolarization. In contrast, I_to in rodents is a major repolarizing current throughout the comparatively short cardiac action potential (Figure, panel A) necessary to maintain extremely high heart rates. I_to is composed of at least two components in the mammalian ventricle. One component is characterized by a slow recovery from inactivation (I_tos), another by a relatively fast recovery from inactivation (I_tof). Comparison of native currents and heterologously expressed channels indicates that I_tof is mediated by Kv4.2 and/or Kv4.3 channels, whereas I_tos is mediated by Kv1.4 channels.

View larger version (28K): [in this window] [in a new window]   Reduction of Itof prolongs APD and may induce hypertrophy via a calcineurin-dependent signaling pathway. A, At physiologically relevant heart rates, Itof is the major repolarizing current of the ventricular action . . . [Full Text of this Article]

This article has been cited by other articles:

				K. Rivard, V. Trepanier-Boulay, H. Rindt, and C. Fiset Electrical remodeling in a transgenic mouse model of {alpha}1B-adrenergic receptor overexpression Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H704 - H718. [Abstract] [Full Text] [PDF]

				Z. Lu, J.-i. Abe, J. Taunton, Y. Lu, T. Shishido, C. McClain, C. Yan, S. P. Xu, T. M. Spangenberg, and H. Xu Reactive Oxygen Species-Induced Activation of p90 Ribosomal S6 Kinase Prolongs Cardiac Repolarization Through Inhibiting Outward K+ Channel Activity Circ. Res., August 1, 2008; 103(3): 269 - 278. [Abstract] [Full Text] [PDF]

				C. M. Wolf, I. P. G. Moskowitz, S. Arno, D. M. Branco, C. Semsarian, S. A. Bernstein, M. Peterson, M. Maida, G. E. Morley, G. Fishman, et al. Somatic events modify hypertrophic cardiomyopathy pathology and link hypertrophy to arrhythmia PNAS, December 13, 2005; 102(50): 18123 - 18128. [Abstract] [Full Text] [PDF]

				D. Lebeche, R. Kaprielian, F. del Monte, G. Tomaselli, J. K. Gwathmey, A. Schwartz, and R. J. Hajjar In Vivo Cardiac Gene Transfer of Kv4.3 Abrogates the Hypertrophic Response in Rats After Aortic Stenosis Circulation, November 30, 2004; 110(22): 3435 - 3443. [Abstract] [Full Text] [PDF]

				S. G. Birnbaum, A. W. Varga, L.-L. Yuan, A. E. Anderson, J. D. Sweatt, and L. A. Schrader Structure and Function of Kv4-Family Transient Potassium Channels Physiol Rev, July 1, 2004; 84(3): 803 - 833. [Abstract] [Full Text] [PDF]

				W. Dun, P. Chandra, P. Danilo Jr., M. R. Rosen, and P. A. Boyden Chronic atrial fibrillation does not further decrease outward currents. It increases them. Am J Physiol Heart Circ Physiol, October 1, 2003; 285(4): H1378 - H1384. [Abstract] [Full Text] [PDF]