Dual regulation of calcium mobilization by inositol 1,4, 5-trisphosphate in a living cell.
Changes in cytosolic free calcium ([Ca(2+)](i)) often take the form of a sustained response or repetitive oscillations. The frequency and amplitude of [Ca(2+)](i) oscillations are essential for the selective stimulation of gene expression and for enzyme activation. However, the mechanism that determines whether [Ca(2+)](i) oscillates at a particular frequency or becomes a sustained response is poorly understood. We find that [Ca(2+)](i) oscillations in rat megakaryocytes, as in other cells, results from a Ca(2+)-dependent inhibition of inositol 1,4,5-trisphosphate (IP(3))-induced Ca(2+) release. Moreover, we find that this inhibition becomes progressively less effective with higher IP(3) concentrations. We suggest that disinhibition, by increasing IP(3) concentration, of Ca(2+)-dependent inhibition is a common mechanism for the regulation of [Ca(2+)](i) oscillations in cells containing IP(3)-sensitive Ca(2+) stores.
Tertyshnikova
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S
Department of Physiology, University of Connecticut Health Center, Farmington, Connecticut 06030-3505, USA.
Fein
A
A
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D008301:Maleimides / Q000494:pharmacology; D008533:Megakaryocytes / Q000187:drug effects / Q000378:metabolism*; D010782:Photolysis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats
D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D000244:Adenosine Diphosphate; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D002118:Calcium