Temporal relationships between Ca2+ store mobilization and Ca2+ entry in an exocrine cell.
Consideration of the principal current models for agonist-induced activation of Ca2+ entry in electrically non-excitable cells suggests that it may be possible to distinguish between them on the basis of predicted differences in the temporal relationship(s) between intracellular Ca2+ release and the activation of Ca2+ entry. Measurements of changes in [Ca2+]i and Mn2+ quench in individual exocrine cells from the avian nasal gland indicate that, whereas Ins(1,4,5)P3-induced release of intracellular Ca2+ occurs within 3-5 s, the increase in Mn2+ quench is delayed by some 20-30 s. Mn2+ quench rate is similarly increased by thapsigargin, and is blocked by SK&F 96365, indicating that the increased Mn2+ quench observed genuinely reflects agonist-enhanced activity of the divalent cation entry pathway normally traversed by Ca2+. Additional experiments indicate that the observed delay is not due to inhibition of this pathway by elevated [Ca2+]i. Furthermore, the delay cannot be explained by the time required for Ins(1,3,4,5)P4 generation, which is essentially maximal within 10 s of agonist addition. It is concluded that the observed delay in the activation of the Ca2+ entry pathway is best explained by 'capacitative' models where increased entry requires the generation, and transmission to the plasma membrane, of an unknown messenger as a direct result of the depletion of intracellular Ca2+ stores.
Shuttleworth
T J
TJ
Department of Physiology, University of Rochester School of Medicine and Dentistry, New York.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002217:Carbachol / Q000494:pharmacology; D004372:Ducks; D005456:Fluorescent Dyes; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D017136:Ion Transport / Q000187:drug effects*; D008345:Manganese; D012491:Salt Gland / Q000166:cytology / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D005456:Fluorescent Dyes; D007093:Imidazoles; D007211:Indoles; D013729:Terpenes; D008345:Manganese; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D000252:Calcium-Transporting ATPases; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; C048960:indo-1; D002118:Calcium