IMR Press / FBL / Volume 7 / Issue 4 / DOI: 10.2741/A885

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Calcium signaling between sarcolemmal calcium channels and ryanodine receptors in heart cells
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1 Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA
Academic Editor:Hector Valdivia
Front. Biosci. (Landmark Ed) 2002, 7(4), 1867–1878;
Published: 1 September 2002
(This article belongs to the Special Issue The structure and function of calcium release channels)

Cardiac excitation-Ca2+ release coupling is, in essence, a tale of two molecules, sarcolemmal voltage-gated L-type Ca2+ channels (LCCs) and intracellular ryanodine receptors (RyRs), communicating via the Ca2+-induced Ca2+ release mechanism. Recent advances have provided a microscopic view of the intermolecular Ca2+ signaling between LCCs and RyRs. In a dyadic junction or a "couplon", LCCs open and close stochastically upon depolarization, delivering a train of high local Ca2+ pulses ("Ca2+ sparklets") to the RyRs in the abutting SR terminal cisternae. Stochastic activation of RyRs discharges "Ca2+ sparks" from different couplons, which summate into global Ca2+ transients. Hence, ignition of Ca2+ sparks by Ca2+ sparklets constitute elementary events of EC coupling. While the sparklet-spark coupling is of low fidelity (at 0 mV, about one out of 50 sparklets triggers a spark under physiological conditions), the high-gain amplification of CICR (approximately 15 at 0 mV) is achieved because of the greater single-channel flux and open time of RyRs and multi-RyR origin of Ca2+ spark. The global stability of CICR is safeguarded by many factors acting in synergy, including physical separation of RyR clusters, sheer Ca2+ gradients around the channel pores, low intrinsic Ca2+ sensitivity of RyRs in vivo, and high cooperativity for the Ca2+-dependent spark activation. The local stability of CICR is insured because of strong, use-dependent inactivation of RyRs, that terminates Ca2+ sparks and confers persistent local SR refractoriness.

Ryanodine Receptors
Ca2+ Sparks
Excitation-Contraction Coupling
Ca2+-induced Ca2+ Release
Local Control Theory
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