This review highlights how spatial and temporal integration of localized calcium sparks and oscillations regulates global intracellular calcium levels and smooth muscle contractility.
The multiplicity of mechanisms involved in regulation of intracellular Ca(2+) concentration (Ca(2+)(i)) in smooth muscle results in both intra- and intercellular heterogeneities in Ca(2+)(i). Heterogeneity in Ca(2+)(i) regulation is reflected by the presence of spontaneous, localized Ca(2+)(i) transients (Ca(2+) sparks) representing Ca(2+) release through ryanodine receptor (RyR) channels. Ca(2+) sparks display variable spatial Ca(2+) distributions with every occurrence within and across cellular regions. Individual sparks are often grouped, and fusion of sparks produces large local elevations in Ca(2+)(i) that occasionally trigger propagating Ca(2+)(i) waves. Ca(2+) 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(2+)(i) oscillations that originate from foci with high spark incidence and also represent Ca(2+) release through RyR channels. With increasing agonist concentration, the peak of regional Ca(2+)(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(2+)(i), representing a spatial and temporal integration of the oscillations. The significance of agonist-induced Ca(2+)(i) oscillations lies in the establishment of a global Ca(2+)(i) level for slower Ca(2+)-dependent physiological processes.
Pabelick et al. (Sun,) studied this question.