Calcium-induced calcium release (CICR) has been observed in cardiac myocytes as elementary calcium release events (calcium sparks) associated with the opening of L-type Ca 2+ channels. In heart cells, a tight coupling between the gating of single L-type Ca 2+ channels and ryanodine receptors (RYRs) underlies calcium release. Here we demonstrate that L-type Ca 2+ channels activate RYRs to produce CICR in smooth muscle cells in the form of Ca 2+ sparks and propagated Ca 2+ waves. However, unlike CICR in cardiac muscle, RYR channel opening is not tightly linked to the gating of L-type Ca 2+ channels. L-type Ca 2+ channels can open without triggering Ca 2+ sparks and triggered Ca 2+ sparks are often observed after channel closure. CICR is a function of the net flux of Ca 2+ ions into the cytosol, rather than the single channel amplitude of L-type Ca 2+ channels. Moreover, unlike CICR in striated muscle, calcium release is completely eliminated by cytosolic calcium buffering. Thus, L-type Ca 2+ channels are loosely coupled to RYR through an increase in global Ca 2+ due to an increase in the effective distance between L-type Ca 2+ channels and RYR, resulting in an uncoupling of the obligate relationship that exists in striated muscle between the action potential and calcium release. calcium-induced calcium release smooth muscle Ca 2+ sparks excitation–contraction coupling action potential signaling Footnotes The online version of this article contains supplemental material. Abbreviations used in this paper: CICR, calcium-induced calcium release; E-C, excitation–contraction; RYR, ryanodine receptor; SR, sarcoplasmic reticulum. Submitted: 30 August 1999 Revision requested 28 March 2000 Accepted: 28 March 2000
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Calcium-Induced Calcium Release in Smooth Muscle
Collier, M.L.; Ji, G.; Wang, Y.-X.; Kotlikoff, M.I.
Follow The Journal of General Physiology
, Volume 115 (5): 653
Rockefeller University Press – May 1, 2000
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