Regulation of the secretory response in bovine chromaffin cells.

The nicotine-induced current and the Ca2+ current were studied in cultured bovine chromaffin cells using the whole cell patch-clamp technique. The dose-response curve for the nicotinic current gave a dissociation constant of 53 microM and a Hill coefficient of 1.3. Desensitization of the nicotinic current was rapid, with time constants of 22 and 155 ms at 10 microM nicotine. At higher concentrations of nicotine, both time constants decreased somewhat, but the most prominent effect was on the ratio of the two components. Recovery from desensitization was fitted by a single exponential with a time constant of approximately 6 s. Ca2+ current and catecholamine secretion were highly sensitive to changes in extracellular H+ concentration ([H+]o), such that small increases in [H+]o markedly decreased both. The Ca2+ current measured in a chromaffin cell located within a cluster of cells, but not in a single isolated cell, was markedly suppressed when KCl or nicotine was used to induce secretion, suggesting possible local feedback of secretory agents. Among agents secreted by chromaffin cells, ATP, enkephalins, epinephrine, and protons, only protons significantly suppressed the Ca2+ current. Our findings suggest that the secretory response of chromaffin cells may be modulated by rapid desensitization of the nicotinic receptor and a secretion-dependent suppression of the Ca2+ current.