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(Circulation Research. 2006;98:1232.)
© 2006 American Heart Association, Inc.

Editorials

Is the Ryanodine Receptor a Target for Antiarrhythmic Therapy?

Christian Pott, Joshua I. Goldhaber

From the Departments of Physiology and Medicine and the Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, Calif.

Correspondence to Joshua I. Goldhaber, MD, David Geffen School of Medicine at UCLA, Cardiology, BH-407 CHS, 10833 LeConte Ave, Los Angeles, CA 90095. E-mail jgoldhaber@mednet.ucla.edu

See related article, pages 1299–1305

Key Words: arrhythmias • calcium • sarcoplasmic reticulum • sodium-calcium exchange • tetracaine

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

In cardiac myocytes, Ca²⁺ influx and efflux must be in balance to ensure cellular viability, normal contractile function, and a stable heart rhythm. Therefore Ca²⁺ fluxes between the major cellular compartments and the extracellular space have to adapt to a wide range of changing conditions. Failure to do so can result in Ca²⁺ overload of the sarcoplasmic reticulum (SR), leading to arrhythmogenic spontaneous release of SR Ca²⁺ by ryanodine receptors (RyRs). Recently, it was shown that suppressing RyR open probability (P_o) was protective in a mouse model of a congenital arrhythmia caused by increased Ca²⁺ leak from RyRs. It was suggested that such a strategy could be applied more widely to treat patients with common ventricular arrhythmias.¹ Is it possible to suppress SR Ca²⁺ release without jeopardizing contractile function and aggravating Ca²⁺ overload?

In this issue of Circulation Research, Venetucci et al² answer this question by using the analytic techniques they have used so successfully in the past to examine Ca²⁺ fluxes and autoregulation in normal cells.³ Their surprising finding is that reducing RyR Po in Ca²⁺-overloaded myocytes not only suppresses arrhythmogenic spontaneous Ca²⁺ release, but also increases the amplitude of the Ca²⁺ transient while maintaining Ca²⁺ homeostasis. To fully appreciate this finding, it is essential to review the profile of Ca²⁺ fluxes under both physiological conditions and during arrhythmogenic events.

Under normal conditions, Ca²⁺ enters the cardiomyocyte at the beginning of each contractile cycle through L-type Ca²⁺ channels (LCCs) and minimally raises the cytoplasmic Ca²⁺ concentration. . . . [Full Text of this Article]

Related Article:

Reducing Ryanodine Receptor Open Probability as a Means to Abolish Spontaneous Ca²⁺ Release and Increase Ca²⁺ Transient Amplitude in Adult Ventricular Myocytes

L.A. Venetucci, A.W. Trafford, M.E. Díaz, S.C. O’Neill, and D.A. Eisner
Circ. Res. 2006 98: 1299-1305. [Abstract] [Full Text] [PDF]