Ca2+ influx drives agonist‐activated [Ca2+]i oscillations in an exocrine cell

Abstract

In current models describing agonist-induced oscillations in [Ca ²⁺]_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 detectible 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.