Time-dependent modulation of capacitative Ca2+ entry signals by plasma membrane Ca2+ pump in endothelium.
In vascular endothelial cells, depletion of intracellular Ca2+ stores elicited capacitative Ca2+ entry (CCE) that resulted in biphasic changes of intracellular Ca2+ concentration ([Ca2+]i) with a rapid initial peak of [Ca2+]i followed by a gradual decrease to a sustained plateau level. We investigated the rates of Ca2+ entry, removal, and sequestration during activation of CCE and their respective contributions to the biphasic changes of [Ca2+]i. Ca2+ buffering by mitochondria, removal by Na+/Ca2+ exchange, and a fixed electrical driving force for Ca2+ (voltage-clamp experiments) had little effect on the CCE signal. The rates of entry of Mn2+ and Ba2+, used as unidirectional substitutes for Ca2+ entry through the CCE pathway, were constant and did not follow the concomitant changes of [Ca2+]i. Pharmacological inhibition of the plasma membrane Ca2+ pump, however, abolished the secondary decay phase of the CCE transient. The disparity between the biphasic changes of [Ca2+]i and the constant rate of Ca2+ entry during CCE was the result of a delayed, Ca(2+)-dependent activation of the pump. These results suggest an important modulatory role of the plasma membrane Ca2+ pump in the net cellular gain of Ca2+ during CCE.
Klishin
A
A
Department of Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, USA.
Sedova
M
M
Blatter
L A
LA
D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002413:Cations, Divalent / Q000493:pharmacokinetics; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D013997:Time Factors
D002021:Buffers; D002413:Cations, Divalent; D019831:Sodium-Calcium Exchanger; D000252:Calcium-Transporting ATPases; D002118:Calcium