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(Circulation Research. 2002;91:e3.)
© 2002 American Heart Association, Inc.

Letters to the Editor

Novel Perspectives on the Beating Rate of the Heart

Tatiana M. Vinogradova, Konstantin Yu. Bogdanov, Edward G. Lakatta

Laboratory of Cardiovascular Sciences, National Institute on Aging, Gerontology Research Center, Baltimore, Md, lakattae@grc.nia.nih.gov

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

To the Editor:

Recent studies^1–3 have demonstrated that local Ca²⁺ release during the later part of diastolic depolarization (DD) via ryanodine receptors (RyRs) in the sinoatrial nodal cells (SANCs) activates the electrogenic Na⁺-Ca²⁺ exchanger (NCX). The resultant inward current enhances the rate of DD, leading to an earlier occurrence of the subsequent action potential, ie, to an increase in the beating rate.³ Thus, a beating rate is a result of synchronization of two "ionic generators": (1) a set of sarcolemmal ionic channels and (2) an array of RyRs, which, when activated, can generate rhythmic oscillations of intracellular [Ca²⁺].

Other recent studies indicate that the effect ß-adrenergic receptor (ß-AR) stimulation to enhance the rate of DD and to increase the beating rate requires intact RyR function.^4,5 Specifically, ß-AR stimulation by isoproterenol recruits additional RyRs to release Ca²⁺ during DD; this activates NCX current and increases the rate of DD.⁵ Partial inhibition of normal RyR function by ryanodine, which results in sarcoplasmic reticulum Ca²⁺ depletion, blunts the dose response of isoproterenol to increase the beating rate.⁵

DiFrancesco and Robinson⁶ point out that prior studies have indicated that ß-AR receptor stimulation augments the hyperpolarization-activated current, I_f, in SANCs. While this indeed may be the case, the real issue at hand is to what extent a change in I_f relates to a change in the beating rate. In our experiments, the contribution of I_f to the beating rate either in control conditions or during ß-AR stimulation was minimal compared with the effect of suppression . . . [Full Text of this Article]