ACTIVATION OF NICOTINIC ACETYLCHOLINE-RECEPTORS AUGMENTS CALCIUM CHANNEL-MEDIATED EXOCYTOSIS IN RAT PHEOCHROMOCYTOMA (PC12) CELLS

The functional effect of activating Ca2+-permeable neuronal nicotinic acetylcholine receptors (nAChRs) on vesicle secretion was studied in P C12 cells. Single cells were patch-clamped in the whole-cell configura tion and stimulated with either brief pulses of nicotine to activate t he Ca2+-permeable nACHRs or with voltage steps to activate voltage-dep endent Ca2+ channels. Membrane capacitance was used as a measure of ve sicle secretion. Activation of nAChRs by nicotine application to cells voltage clamped at -80 mV evoked secretion. This secretion was comple tely abolished by nicotinic antagonists. When the cells were voltage c lamped at +20 mV in the presence of Cd2+ to block voltage-activated Ca 2+ channels, nicotine elicited a small amount of secretion. Most inter estingly, when the nAChRs were activated coincidentally with voltage-d ependent Ca2+ channels, secretion was augmented approximately twofold over the secretion elicited with voltage-dependent Ca2+ channels alone . Our data suggest that Ca2+ influx via nAChRs affects Ca2+-dependent cellular functions, including vesicle secretion. In addition to the se cretion evoked by nAChR activation at hyperpolarized potentials, we de monstrate that even at depolarized potentials, nAChRs provide an impor tant Ca2+ entry pathway underlying Ca2+-dependent cellular processes s uch as exocytosis.