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

Summary

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⁺ (K_Ca) channels (STOCs) function as “elementary” Ca²⁺ release units that regulate arterial mygenic tone. Whereas increases in the global [Ca²⁺]_i induce sustained constriction of arterial smooth muscle, Ca²⁺ sparks induce vasodilation through the local activation of K_Ca channels. In cerebral arteries, the global bulk [Ca²⁺]_i and a Ca²⁺ spark frequency < 10^-2 Hz/cell do not cause sufficient K_Ca channel 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.