Ca2+ influx drives agonist-activated [Ca2+]i oscillations in an exocrine cell.
In current models describing agonist-induced oscillations in [Ca2+]i, Ca2+ entry is generally assumed to have a simple sustaining role, replenishing Ca2+ lost from the cell and recharging intracellular Ca2+ stores. In cells from the avian nasal gland, a model exocrine cell, we show that inhibition of Ca2+ entry by La3+, SK&F 96365, or by membrane depolarization, rapidly blocks [Ca2+]i oscillations but does so without detectable depletion of agonist-sensitive Ca2+ stores. As the rate of Mn2+ quenching during [Ca2+]i oscillations is constant, Ca2+ entry is not directly contributing to the [Ca2+]i changes and, instead, appears to be involved in inducing the repetitive release of Ca2+ from internal stores. Together, these data contradict current models in that (i) at the low agonist concentrations where [Ca2+]i oscillations are seen, generated levels of Ins(1,4,5)P3 are themselves inadequate to result in a regenerative [Ca2+]i signal, and (ii) Ca2+ entry is necessary to actually drive the intrinsic oscillatory mechanism.
Martin
S C
SC
Department of Physiology, University of Rochester School of Medicine and Dentistry, NY 14642.
Shuttleworth
T J
TJ
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D004372:Ducks; D005088:Exocrine Glands / Q000166:cytology* / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D007811:Lanthanum / Q000494:pharmacology; D008564:Membrane Potentials
D007093:Imidazoles; D007811:Lanthanum; D002217:Carbachol; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium