Pharmacology of nicotine-induced increase in cytosolic Ca2+ concentrations in chick embryo ciliary ganglion cells.

Chick embryo ciliary ganglion cells were acutely isolated, and the mechanism(s) underlying the increase in the cytosolic Ca2+ concentration ([Ca]in) induced by high concentrations of nicotine examined using fura-2 microfluorometry. The order of potencies of nicotinic receptor agonists in increasing [Ca]in was ACh > nicotine = dimethylphenylpiperazinium > cytisine. The nicotine-induced increase in [Ca]in was inhibited not only by nicotinic antagonists but also by muscarinic antagonists, while the muscarine-induced [Ca]in increase was little affected by nicotinic antagonists. The nicotine-induced [Ca]in increase was inhibited by both L- and N-type Ca2+ channel blockers and potentiated by an L-type Ca2+ channel agonist, Bay-K-8644. Nicotine also increased the cytosolic Na+ concentration ([Na]in) as measured by sodium binding benzofuranisophthalate microfluorometry, and this [Na]in increase was inhibited by various agents which reportedly affected nicotinic receptor channels in adrenal chromaffin cells. These results suggest that nicotine increased Na+ influx through nicotinic receptor channels resulting in membrane depolarization, which in turn increased Ca2+ influx through voltage-dependent Ca2+ channels. However, nicotine still increased influxes of Ca2+ and Mn2+ in the absence of external Na+, suggesting that nicotinic receptor channels in these cells are permeable not only to monovalent cations but also to Ca2+ and Mn2+.