INOSITOL 1,3,4,5-TETRAKISPHOSPHATE ACTIVATES AN ENDOTHELIAL CA2+-PERMEABLE CHANNEL

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 stores 1 by opening a Ca2+-permeable channel in the endoplasmic reticulum 2-4. 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 cells 5,6, 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.