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 Ca(2+)-activated K+ (KCa) channels (STOCs) function as "elementary" Ca2+ release units that regulate arterial myogenic tone. Whereas increases in the global [Ca2+]i induce sustained constriction of arterial smooth muscle, Ca2+ sparks induce vasodilation through the local activation of KCa channels. In cerebral arteries, the global bulk [Ca2+]i and a Ca2+ spark frequency < 10(-2) Hz/cell do not cause sufficient KCa 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.
Gollasch
M
M
Franz Volhard Clinic, Humboldt University Berlin, Germany. gollasch@fvk-berlin.de
Löhn
M
M
Fürstenau
M
M
Nelson
M T
MT
Luft
F C
FC
Haller
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D003326:Coronary Circulation / Q000502:physiology; D006801:Humans; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D014655:Vascular Resistance / Q000502:physiology*
D015220:Calcium Channels; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium