Origin and mechanisms of Ca2+ waves in smooth muscle as revealed by localized photolysis of caged inositol 1,4,5-trisphosphate

McCarron, J.G. and MacMillan, D. and Bradley, K.N. and Chalmers, S. and Muir, T.C. (2004) Origin and mechanisms of Ca2+ waves in smooth muscle as revealed by localized photolysis of caged inositol 1,4,5-trisphosphate. Journal of Biological Chemistry, 279. pp. 8417-8427. ISSN 1083-351X (https://doi.org/10.1074/jbc.M311797200)

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Abstract

The cytosolic Ca2+ concentration ([Ca2+]c) controls diverse cellular events via various Ca2+ signaling patterns; the latter are influenced by the method of cell activation. Here, in single-voltage clamped smooth muscle cells, sarcolemma depolarization generated uniform increases in [Ca2+]c throughout the cell entirely by Ca2+ influx. On the other hand, the Ca2+ signal produced by InsP3-generating agonists was a propagated wave. Using localized uncaged InsP3, the forward movement of the Ca2+ wave arose from Ca2+-induced Ca2+ release at the InsP3 receptor (InsP3R) without ryanodine receptor involvement. The decline in [Ca2+]c (the back of the wave) occurred from a functional compartmentalization of the store, which rendered the site of InsP3-mediated Ca2+ release, and only this site, refractory to the phosphoinositide. The functional compartmentalization arose by a localized feedback deactivation of InsP3 receptors produced by an increased [Ca2+]c rather than a reduced luminal [Ca2+] or an increased cytoplasmic [InsP3]. The deactivation of the InsP3 receptor was delayed in onset, compared with the time of the rise in [Ca2+]c, persisted (>30 s) even when [Ca2+]c had regained resting levels, and was not prevented by kinase or phosphatase inhibitors. Thus different forms of cell activation generate distinct Ca2+ signaling patterns in smooth muscle. Sarcolemma Ca2+ entry increases [Ca2+]c uniformly; agonists activate InsP3R and produce Ca2+ waves. Waves progress by Ca2+-induced Ca2+ release at InsP3R, and persistent Ca2+-dependent inhibition of InsP3R accounts for the decline in [Ca2+]c at the back of the wave.

ORCID iDs

McCarron, J.G. ORCID logoORCID: https://orcid.org/0000-0002-3302-3984, MacMillan, D., Bradley, K.N., Chalmers, S. ORCID logoORCID: https://orcid.org/0000-0002-8073-7576 and Muir, T.C.;
CORE (COnnecting REpositories)