Okadaic acid uncouples calcium entry from depletion of intracellular stores.
The mechanism by which the depletion of intracellular Ca2+ stores stimulates Ca2+ influx is poorly understood. However, the coupling of depletion to influx is broken during mitosis [Preston, S.F. et. al., (1991) Cell Regul., 2, 915-925]. Thus, in interphase HeLa cells, activation of the histamine H1 receptor, or incubation with thapsigargin, which inhibits the Ca(2+)-ATPase of storage vesicles and depletes Ca2+ stores, strongly stimulate Ca2+ influx. In mitotic cells, however, neither histamine nor thapsigargin stimulate Ca2+ influx. Since it has been found that okadaic acid treatment of interphase cells induces a mitotic-like state with respect to a number of other membrane processes, we have asked if okadaic acid might also uncouple Ca2+ depletion from stimulated influx. We show that okadaic acid specifically does suppress this coupling: thapsigargin and histamine deplete stores in control and okadaic-acid-treated HeLa cells, but after treatment with okadaic acid, stimulation of Ca2+ influx is barely detectable. This suggests that a protein phosphorylation/dephosphorylation event controls the coupling of Ca2+ stores to influx, and that there may be a physiological mechanism for control of the Ca2+ response to hormonal signals at the level of coupling.
Department of Physiology, University of Connecticut Health Center, Farmington.
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RD
Berlin
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Preston
D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002451:Cell Compartmentation / Q000187:drug effects; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007399:Interphase; D007424:Intracellular Fluid / Q000187:drug effects* / Q000378:metabolism; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D004988:Ethers, Cyclic; D011969:Receptors, Histamine H1; D013729:Terpenes; D019319:Okadaic Acid; D019284:Thapsigargin; D006632:Histamine; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D000252:Calcium-Transporting ATPases; D002118:Calcium