Receptor-activated calcium entry in exocrine cells does not occur via agonist-sensitive intracellular pools.
Currently, most models describing receptor-activated Ca2+ entry in exocrine cells invoke a pathway for the entry of extracellular Ca2+ directly linking the agonist-sensitive intracellular Ca2+ pools with the plasma membrane. In the avian nasal gland, a model exocrine ion-secreting tissue, we have found that Ca2+ entry during refilling of the intracellular pools following termination of receptor activation (by atropine) occurs via the cytoplasm and not directly into the empty pools. Under appropriate conditions this can be demonstrated as a transient increase in [Ca2+]i (intracellular Ca2+ concn.) seen on restoration of normal extracellular Ca2+ concentrations after atropine to stimulated cells whose intracellular stores have been prevented from refilling by incubation in a low-extracellular-Ca2+ medium. The magnitude of these [Ca2+]i transients decays with time, but with a time course markedly slower than for the corresponding decrease in intracellular Ins(1,4,5)P3. Further experiments have revealed that Ca2+ entry into the cytoplasm during the initial stimulation phase is also direct and not via the intracellular pools. Thus the initial rates of increase in [Ca2+]i during stimulation are always faster in conditions where both Ca2+ entry and Ca2+ release occur (i.e. they are additive). These differences could not be explained by any effects of extracellular Ca2+ on the initial increases in intracellular Ins(1,4,5)P3 after addition of carbachol. These data are therefore inconsistent with the current models in which the rate of Ca2+ entry through the agonist-sensitive pools cannot exceed the rate of Ca2+ release. It appears therefore that Ca2+ entry and Ca2+ release must occur via separate pathways operating in parallel, and not in series as previously predicted.
Shuttleworth
T J
TJ
Department of Physiology, Box 642, University of Rochester School of Medicine and Dentistry, NY 14642.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D004372:Ducks; D007294:Inositol / Q000031:analogs & derivatives / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000031:analogs & derivatives; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009296:Nasal Cavity / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009946:Organothiophosphorus Compounds / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012491:Salt Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D009946:Organothiophosphorus Compounds; D011976:Receptors, Muscarinic; C054737:inositol 1,4,5-triphosphorothioate; D007294:Inositol; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D002118:Calcium