Signal transduction in smooth muscle - Invited Review: Significance of spatial and temporal heterogeneity of calcium transients in smooth muscle

The multiplicity of mechanisms involved in regulation of intracellular Ca2+ concentration ([ Ca2+](i)) in smooth muscle results in both intra- and intercellular heterogeneities in [Ca2+](i). Heterogeneity in [Ca2+](i) regulation is reflected by the presence of spontaneous, localized [Ca2+](i) transients (Ca2+ sparks) representing Ca2+ release through ryanodine receptor (RyR) channels. Ca2+ sparks display variable spatial Ca2+ distributions with every occurrence within and across cellular regions. Individual sparks are often grouped, and fusion of sparks produces large local elevations in [Ca2+](i) that occasionally trigger propagating [Ca2+](i) waves. Ca2+ 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 [Ca2+](i) oscillations that originate from foci with high spark incidence and also represent Ca2+ release through RyR channels. With increasing agonist concentration, the peak of regional [Ca2+](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 [Ca2+](i), representing a spatial and temporal integration of the oscillations. The significance of agonist-induced [Ca2+](i) oscillations lies in the establishment of a global [Ca2+](i) level for slower Ca2+-dependent physiological processes.