Inositol 1,3,4,5-tetrakisphosphate activates an endothelial Ca(2+)-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 by opening a Ca(2+)-permeable channel in the endoplasmic reticulum. 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 Ca(2+)-sensitive Ca(2+)-permeable channel in endothelial cells. We find that InsP4, which induces Ca2+ influx into acinar cells, enhances the activity of the Ca(2+)-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.
Lückhoff
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Department of Pharmacology, Mayo Foundation, Rochester 55905.
Clapham
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D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D008345:Manganese / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects
D015220:Calcium Channels; D008345:Manganese; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D001920:Bradykinin; D002118:Calcium