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 Pieske, B. Articles by Kockskämper, J. Search for Related Content PubMed PubMed Citation Articles by Pieske, B. Articles by Kockskämper, J. Related Collections Calcium cycling/excitation-contraction coupling

(Circulation Research. 2002;91:553.)
© 2002 American Heart Association, Inc.

Editorials

Alternans Goes Subcellular

A "Disease" of the Ryanodine Receptor?

Burkert Pieske, Jens Kockskämper

From the Department of Cardiology and Pneumology, University of Göttingen, Germany.

Correspondence to Priv-Doz Dr Burkert Pieske, Dept of Cardiology and Pneumology, University of Göttingen, Robert-Koch-Str 40, 37075 Göttingen, Germany. E-mail pieske@med.uni-goettingen.de

Key Words: alternans • ventricular fibrillation • ryanodine receptor

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

In 1872 Traube¹ first described pulsus alternans, a regular beat-to-beat alternation of the strength of the heartbeat. Since then, cardiologists and physiologists have learned that cardiac alternans can come in many flavors: as mechanical, electrical, or [Ca²⁺]_i transient alternans (Ca²⁺ alternans).² They also had to realize that alternans is a life-threatening condition, less so because of impaired cardiac output but because it can lead to ventricular fibrillation (VF) and sudden cardiac death. How exactly electromechanical alternations of the heartbeat can cause VF has long been an open question. A leap forward came recently with an elegant study on electrical (T-wave) alternans in guinea-pig hearts.³ It was shown that during alternans, neighboring regions within the heart started to alternate out-of-phase with each other (discordant alternans). Such discordant electrical alternans, if sufficient in magnitude, led to unidirectional block and reentry, thereby causing VF.

Ca²⁺ Alternans: The Heart of the Problem

Despite recent advances in our understanding of the mechanisms linking electromechanical alternans to VF, the crucial question still remains: how does alternans develop in the first place? The study of cellular Ca²⁺ alternans might help answer this question because Ca²⁺ alternans lies at the heart of the problem. It causes both mechanical alternans (by activation of the myofilaments) and electrical alternans (by modulation of Ca²⁺-dependent membrane currents). Experimental interventions aimed at disabling sarcoplasmic reticulum (SR) Ca²⁺ release abolish electromechanical alternans.⁴ Furthermore, enhancement of sarcolemmal Ca²⁺ influx and/or SR Ca²⁺ load and release can reverse alternans.^5,6 Thus, modulation of the SR Ca²⁺ release process is somehow critically involved . . . [Full Text of this Article]

This article has been cited by other articles:

				D. Jiang, W. Chen, R. Wang, L. Zhang, and S. R. W. Chen Loss of luminal Ca2+ activation in the cardiac ryanodine receptor is associated with ventricular fibrillation and sudden death PNAS, November 13, 2007; 104(46): 18309 - 18314. [Abstract] [Full Text] [PDF]

				K. R. Sipido Understanding Cardiac Alternans: The Answer Lies in the Ca2+ Store Circ. Res., March 19, 2004; 94(5): 570 - 572. [Full Text] [PDF]

				M. C. Sanguinetti and P. B. Bennett Antiarrhythmic Drug Target Choices and Screening Circ. Res., September 19, 2003; 93(6): 491 - 499. [Abstract] [Full Text] [PDF]

				A. V Zima, J. Kockskamper, R. Mejia-Alvarez, and L. A Blatter Pyruvate Modulates Cardiac Sarcoplasmic Reticulum Ca2+ Release in Rats Via Mitochondria-Dependent and -Independent Mechanisms J. Physiol., August 1, 2003; 550(3): 765 - 783. [Abstract] [Full Text] [PDF]