TEMPORAL RELATIONSHIPS BETWEEN CA2+ STORE MOBILIZATION AND CA2+ ENTRYIN AN EXOCRINE CELL

Consideration of the principal current models for agonist-induced acti vation of Ca2+ entry in electrically non-excitable cells suggests that it may be possible to distinguish between them on the basis of predic ted 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 av ian nasal grand indicate that, whereas Ins(1,4,5)P-3-induced release o f 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 incre ased Mn2+ quench observed genuinely reflects agonist-enhanced activity of the divalent cation entry pathway normally traversed by Ca2+ Addit ional experiments indicate that the observed delay is not due to inhib ition of this pathway by elevated [Ca2+](i). Furthermore, the delay ca nnot be explained by the time required for Ins(1,3,4,5)P-4 generation, which is essentially maximal within 10 s of agonist addition. It is c oncluded that the observed delay in the activation of the Ca2+ entry p athway is best explained by 'capacitative' models where increased entr y requires the generation, and transmission to the plasma membrane, of an unknown messenger as a direct result of the depletion of intracell ular Ca2+ stores.