Signal Transduction in Smooth Muscle Invited Review: Significance of spatial and temporal heterogeneity of calcium transients in smooth muscle

Pabelick, Christina M., Gary C. Sieck, and Y. S. Prakash. Invited Review: Significance of spatial and temporal heterogeneity of calcium transients in smooth muscle. J Appl Physiol 91: 488–496, 2001.—The multiplicity of mechanisms involved in regulation of intracellular Ca21 concentration ([Ca]i) in smooth muscle results in both intraand intercellular heterogeneities in [Ca]i. Heterogeneity in [Ca]i regulation is reflected by the presence of spontaneous, localized [Ca]i transients (Ca21 sparks) representing Ca21 release through ryanodine receptor (RyR) channels. Ca21 sparks display variable spatial Ca21 distributions with every occurrence within and across cellular regions. Individual sparks are often grouped, and fusion of sparks produces large local elevations in [Ca]i that occasionally trigger propagating [Ca]i waves. Ca21 sparks may modulate membrane potential and thus smooth muscle contractility. Sparks may also be the target of other regulatory factors in smooth muscle. Agonists induce propagating [Ca]i oscillations that originate from foci with high spark incidence and also represent Ca21 release through RyR channels. With increasing agonist concentration, the peak of regional [Ca]i oscillations remains relatively constant, whereas both frequency and propagation velocity increase. In contrast, the global cellular response appears as a concentration-dependent increase in peak as well as mean cellular [Ca]i, representing a spatial and temporal integration of the oscillations. The significance of agonist-induced [Ca]i oscillations lies in the establishment of a global [Ca]i level for slower Ca21-dependent physiological processes.