Ca2+channels, Ca2+sparks, and regulation of arterial smooth muscle function

In cardiac, skeletal, and arterial muscle, transient, spatially localized elevations in [Ca2+]i, termed “Ca2+sparks”, have been observed using confocal laser scanning microscopy. Ca2+sparks are thought to represent “elementary” Ca2+release events, which arise from one or more ryanodine receptor (RyR) channels in the sarcoplasmic reticulum (SR). In striated muscle, Ca2+sparks are thought to be key elements of excitation-contraction coupling. In arterial smooth muscle, Ca2+sparks have been suggested to oppose myogenic vasoconstriction and to influence vasorelaxation. Using a developmental model, we have investigated whether RyRs causing Ca2+sparks and activation of Ca2+-activated K+(KCa) channels (STOCs) function as “elementary” Ca2+release units that regulate arterial mygenic tone. Whereas increases in the global[Ca2+]iinduce sustained constriction of arterial smooth muscle, Ca2+sparks induce vasodilation through the localactivation of KCachannels. In cerebral arteries, the globalbulk [Ca2+]iand a Ca2+spark frequency < 10-2Hz/cell do not cause sufficient KCachannel activity to regulate membrane potential of smooth muscle cells and myogenic tone. The frequency of Ca2+sparks and STOCs is regulated by agents that modulate protein kinase G and protein kinase A activity. Our findings suggest that “elementary” Ca2+release units may represent novel, important therapeutic targets for regulating function of the intact arterial smooth muscle tissue.