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

Abstract

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+]itransients (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.