Abstract

The Ca2+ release activity of inositol 1, 4, 5-trisphosphate receptor (InsP3R) is biphasically dependent on the cytoplasmic Ca2+ concentration: activation near 100 nM and inhibition around 1 μM. We have found that the cytoplasmic Ca2+ concentration is not simply a modulator of InsP3R but is an indispensable factor for channel activation. The Ca2+ requirement of InsP3R places the Ca2+ release channel within a Ca2+-mediated positive feedback loop, which has been demonstrated with caged InsP3 and Ca2+. The positive feedback mechanism seems to be the important basis for the generation of Ca2+ wave in various cell types including smooth muscle cells. To further clarify the role of Ca2+ stores in the smooth muscle function, we measured the Ca2+ concentration in individual smooth muscle cells in isolated vascular tissues stimulated with perivascular sympathetic nerves using a confocal microscope. We observed in these cells Ca2+ waves/oscillations due to Ca2+ release from the stores. These results show that the Ca2+ requirement of InsP3 receptor plays an important role in the regulation of vascular contraction. They also throw new light on both pharmacological and pathophysiological studies of vascular tone.

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