Pharmacology of nicotine-induced increase in cytosolic Ca 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 agonists, 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 resulting in chromaffin cells. These results suggest that nicotine increased Na⁺ influx 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⁺.