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Inositol 1,3,4,5-tetrakisphosphate activates an endothelial Ca2+-permeable channel

Abstract

RECEPTOR-MEDIATED increases in the cytosolic free calcium ion concentration in most mammalian cells result from mobilization of Ca2+ from intracellular stores as well as transmembrane Ca2+ influx. Inositol 1,4,5-trisphosphate (InsP3) releases calcium from intracellular stores1 by opening a Ca2+-permeable channel in the endoplasmic reticulum2–4. But the mechanism and regulation of Ca2+ entry into nonexcitable cells has remained elusive because the entry pathway has not been defined. Here we characterize a novel inositol 1,3,4,5-tetrakisphosphate (InsP4) and Ca2+-sensitive Ca2+-permeable channel in endothelial cells. We find that InsP4, which induces Ca2+ influx into acinar cells5,6, enhances the activity of the Ca2+-permeable channel when exposed to the intracellular surface of endothelial cell inside-out patches. Our results suggest a molecular mechanism which is likely to be important for receptor-mediated Ca2+ entry.

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Lückhoff, A., Clapham, D. Inositol 1,3,4,5-tetrakisphosphate activates an endothelial Ca2+-permeable channel. Nature 355, 356–358 (1992). https://doi.org/10.1038/355356a0

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