Sodium-dependent calcium efflux from adrenal chromaffin cells following exocytosis. Possible role of secretory vesicle membranes.
Although cytosolic Ca2+ transients are known to influence the magnitude and duration of hormone and neurotransmitter release, the processes regulating the decay of such transients after cell stimulation are not well understood. Na(+)-dependent Ca2+ efflux across the secretory vesicle membrane, following its incorporation into the plasma membrane, may play a significant role in Ca2+ efflux after stimulation of secretion. We have measured an enhanced 45Ca2+ efflux from cultured bovine adrenal chromaffin cells following cell stimulation with depolarizing medium (75 mM K+) or nicotine (10 microM). Such stimulation also causes Ca2+ uptake via voltage-gated Ca2+ channels and secretion of catecholamines. Na+ replacement with any of several substitutes (N-methyl-glucamine, Li+, choline, or sucrose) during cell stimulation inhibited the enhanced 45Ca2+ efflux, indicating and Na(+)-dependent Ca2+ efflux process. Na+ deprivation did not inhibit 45Ca2+ uptake or catecholamine secretion evoked by elevated K+. Suppression of exocytotic incorporation of secretory vesicle membranes into the plasma membrane with hypertonic medium (620 mOsm) or by lowering temperature to 12 degrees C inhibited K(+)-stimulated 45Ca2+ efflux in Na(+)-containing medium but did not inhibit the stimulated 45Ca2+ uptake. Enhancement of exocytotic secretion with pertussis toxin resulted in an enhanced 45Ca2+ efflux without affecting calcium uptake. The combined results suggest that Na(+)-dependent Ca2+ efflux across secretory vesicle membranes, following their incorporation into the plasma membrane during exocytosis, plays a significant role in regulating calcium efflux and the decay of cytosolic Ca2+ in adrenal chromaffin cells and possibly in related secretory cells.
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Department of Pharmacology and Toxicology, Albany Medical College, New York 12208.
Schneider
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D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002414:Cations, Monovalent; D002417:Cattle; D002478:Cells, Cultured; D002837:Chromaffin Granules / Q000187:drug effects / Q000378:metabolism*; D005089:Exocytosis; D006982:Hypertonic Solutions; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D009638:Norepinephrine / Q000378:metabolism; D037342:Pertussis Toxin; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology*; D013696:Temperature; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002414:Cations, Monovalent; D006982:Hypertonic Solutions; D010566:Virulence Factors, Bordetella; D012964:Sodium; D037342:Pertussis Toxin; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine