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(Circulation Research. 2006;99:921.)
© 2006 American Heart Association, Inc.

Editorials

The Beat Goes On

Diastolic Noise That Just Won’t Quit

Donald M. Bers

From the Department of Physiology and Cardiovascular Institute, Loyola University Chicago, Stritch School of Medicine, Maywood, Ill.

Correspondence to Donald M. Bers, PhD, Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153. E-mail dbers@lumc.edu

See related article, pages 979–987

Key Words: cardiac electrophysiology • pacemaker • arrhythmias • sarcoplasmic reticulum Na/Ca exchange • excitation-contraction coupling

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

	Introduction

 
In this issue Bogdanov et al¹ show how late diastolic depolarization in rabbit SA-node pacemaker (SAN) cells may be driven largely by stochastic local SR Ca²⁺ release events (LCRs), consequent pulses of inward Na/Ca²⁺ exchange current (I_NCX) and small jumps in membrane potential (E_m). This group has published a comprehensive series of studies (see their reference list) and have made a compelling case for the importance of SR Ca²⁺ release in SAN pacemaker rate, and response to ß-adrenergic activation. The mechanism is as follows (Figure 1). SAN cells have relatively high basal levels of cAMP and phospholamban phosphorylation,² resulting in highly active SR Ca²⁺ uptake. After a prior beat, as SR Ca²⁺ content rises and the ryanodine receptor (RyR) recovers its triggerability, the high luminal [Ca²⁺] causes activation of a cluster of RyRs to produce an LCR or Ca²⁺ spark. The rise in local [Ca²⁺]_i near the Na/Ca²⁺ exchanger activates Ca²⁺ extrusion via inward I_NCX causing depolarization. In particular, these Ca sparks (or LCRs) are known to be very brief stochastic local releases of a bolus of Ca²⁺, which induce an almost simultaneous bolus of inward I_NCX (because of the high local submembrane [Ca²⁺]_i near the NCX).³ Note the simultaneous spikes on the RyR release and I_NCX traces in Figure 2. The high membrane impedance of SAN cells (because of minimal inward rectifier K current I_K1)⁴ allows this brief pulse of inward current to cause a small jump in . . . [Full Text of this Article]

Related Article:

Membrane Potential Fluctuations Resulting From Submembrane Ca²⁺ Releases in Rabbit Sinoatrial Nodal Cells Impart an Exponential Phase to the Late Diastolic Depolarization That Controls Their Chronotropic State

Konstantin Y. Bogdanov, Victor A. Maltsev, Tatiana M. Vinogradova, Alexey E. Lyashkov, Harold A. Spurgeon, Michael D. Stern, and Edward G. Lakatta
Circ. Res. 2006 99: 979-987. [Abstract] [Full Text] [PDF]

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