Calcium-Induced Calcium Release in Smooth Muscle

Abstract

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 Ca2+ channels. In heart cells, a tight coupling between the gating of single L-type Ca2+ channels and ryanodine receptors (RYRs) underlies calcium release. Here we demonstrate that L-type Ca2+ channels activate RYRs to produce CICR in smooth muscle cells in the form of Ca2+ sparks and propagated Ca2+ waves. However, unlike CICR in cardiac muscle, RYR channel opening is not tightly linked to the gating of L-type Ca2+ channels. L-type Ca2+ channels can open without triggering Ca2+ sparks and triggered Ca2+ sparks are often observed after channel closure. CICR is a function of the net flux of Ca2+ ions into the cytosol, rather than the single channel amplitude of L-type Ca2+ channels. Moreover, unlike CICR in striated muscle, calcium release is completely eliminated by cytosolic calcium buffering. Thus, L-type Ca2+ channels are loosely coupled to RYR through an increase in global [Ca2+] due to an increase in the effective distance between L-type Ca2+ channels and RYR, resulting in an uncoupling of the obligate relationship that exists in striated muscle between the action potential and calcium release.

Ca2+oscillations, gradients, and homeostasis in vascular smooth muscle

“…Evidence suggests that in vascular smooth muscle the peripheral SR functions as a superficial buffer barrier rather than amplifying through CICR. Interestingly, in bladder myocytes, where there is direct evidence for CICR (14), the coupling between VGCC and RyR has been found to be of the "loose" type in support of the idea that the VGCC are not part of the PM-SR junctional complexes (6). This is further supported by the structural finding that the Ltype VGCC is localized on the caveolin-rich portion of the PM (8).…”

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

“…The function of RyRs in SMCs is more variable and less well understood (269). In some vessels, RyRs amplify Ca 2+ signals generated by other ion channels contributing to increases in intracellular Ca 2+ and promoting vasoconstriction.…”

Calcium Channels in Vascular Smooth Muscle

“…RyR1 and RyR2 mediate Ca 2+ sparks (e.g., Ca 2+ release from intracellular stores through RyRs) in portal vein SM (Coussin, Macrez, Morel, & Mironneau, 2000), whereas RyR2 has been found to be the predominant isoform in VSM from rat resistance vessels (Vaithianathan et al, 2010). Several studies suggest that in contrast to the tight coupling between LTCCs and RyRs in skeletal and cardiac muscle, a loose coupling mechanism may exist in VSM in which LTCCs indirectly modulate RyRs by contributing to global [Ca 2+ ] i and SR Ca 2+ load (Collier, Ji, Wang, & Kotlikoff, 2000; Essin et al, 2007). Interestingly, recent studies demonstrate that application of Ni 2+ at a concentration that selectively inhibits Ca V 3.2 reduced Ca 2+ spark activity in VSM from WT mice, but had no effect in cells from Ca V 3.2 knockout mice (Harraz, Brett, et al, 2015).…”