Inability of Ca2+ influx through nicotinic ACh receptor channels to stimulate catecholamine secretion in bovine adrenal chromaffin cells: studies with fura-2 and SBFI microfluorometry.

The concentration of cytosolic Ca2+ ([Ca]in) and catecholamine (CA) secretion were examined in bovine adrenal chromaffin cells to determine whether Ca2+ influx through nicotinic ACh receptor (nAChR) channels contributes to CA secretion induced by nAChR stimulation. Nicotine added under Na(+)-free conditions caused a marked increase in [Ca]in and quenching of fura-2 fluorescence in the presence of Mn2+, suggesting the stimulated entry of divalent cations through nAChR channels. However, nicotine-induced increase in CA secretion occurred only at a non-physiologically high external Ca2+ concentration under Na(+)-free conditions. Both the nicotine-induced increase in [Ca]in and CA secretion under Na(+)-free conditions were reduced in the presence of hexamethonium, methoxyverapamil (D600), nifedipine, Bay-K-8644, clonidine, and guanethidine. All of these agents inhibited the nicotine-induced increase in cytosolic Na+ concentration in a dose-dependent manner, as measured by SBFI microfluorometry. The present results suggest that Ca2+ influx through nAChR channels under physiological conditions may not contribute to CA secretion.