Published online before print January 16, 2003, doi: 10.1161/01.RES.0000055920.64384.FB
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Submitted on October 28, 2002
Revised on December 10, 2002
Accepted on December 30, 2002
Cyclic Variation of Intracellular Calcium. A Critical Factor for Cardiac Pacemaker Cell Dominance
Edward G. Lakatta *;
From the Gerontology Research Center, Baltimore, Md.
* To whom correspondence should be addressed. E-mail: LakattaE{at}grc.nia.nih.gov.
While a diversity of cell types and distribution within the sinoatrial node and cell-cell interactions add complexity to a complete elucidation of the heart's pacemaker function, it has become clear that cyclic variation of submembrane [Ca2+] and activation of the Na+-Ca2+ exchanger during diastolic depolarization (DD) act in concert with ion channels to confer on sinoatrial node cells (SANCs) their status of dominance with respect to pacemaker function. Studies using confocal microscopy indicate that subsarcolemmal Ca2+ release via ryanodine receptors occurs not only in response to the action potential (AP) upstroke, but also during the DD, and this is augmented by 
-adrenergic receptor (-AR) stimulation. Spontaneous APs simulated by mathematical SANC models beat at a faster rate when this subsarcolemmal Ca2+ waveform measured under -AR stimulation is introduced into the modeling scheme. Thus, in future investigation of pacemaker functioning in health, disease, and disease therapies the "bar ought to be raised" to embrace the impact of cyclic variation in submembrane [Ca2+] on pacemaker function. The full text of this article is available at http://www.circresaha.org.
Key words: sinoatrial node •
-adrenergic stimulation •
ryanodine receptor •
submembrane Ca2+ release
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