細胞内Ca^<2+> ストアと血管平滑筋収縮 Intracellular Ca^<2+> stores and vascular smooth muscle contraction

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The Ca<SUP>2+</SUP> release activity of inositol 1, 4, 5-trisphosphate receptor (InsP<SUB>3</SUB>R) is biphasically dependent on the cytoplasmic Ca<SUP>2+</SUP> concentration: activation near 100 nM and inhibition around 1 μM. We have found that the cytoplasmic Ca<SUP>2+</SUP> concentration is not simply a modulator of InsP<SUB>3</SUB>R but is an indispensable factor for channel activation. The Ca<SUP>2+</SUP> requirement of InsP<SUB>3</SUB>R places the Ca<SUP>2+</SUP> release channel within a Ca<SUP>2+</SUP>-mediated positive feedback loop, which has been demonstrated with caged InsP<SUB>3</SUB> and Ca<SUP>2+</SUP>. The positive feedback mechanism seems to be the important basis for the generation of Ca<SUP>2+</SUP> wave in various cell types including smooth muscle cells. To further clarify the role of Ca<SUP>2+</SUP> stores in the smooth muscle function, we measured the Ca<SUP>2+</SUP> concentration in individual smooth muscle cells in isolated vascular tissues stimulated with perivascular sympathetic nerves using a confocal microscope. We observed in these cells Ca<SUP>2+</SUP> waves/oscillations due to Ca<SUP>2+</SUP> release from the stores. These results show that the Ca<SUP>2+</SUP> requirement of InsP<SUB>3</SUB> 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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  • 日本薬理学雑誌

    日本薬理学雑誌 106, 41-44, 1995-09-01

    公益社団法人 日本薬理学会

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