Mechanism Underlying the ATP‐Induced Increase in the Cytosolic Ca²⁺ Concentration in Chick Ciliary Ganglion Neurons

Abstract: We examined the mechanism underlying the ATP‐induced increase in the cytosolic Ca²⁺ concentration ([Ca]_in) in acutely isolated chick ciliary ganglion neurons, using fura‐2 microfluorometry. The ATP‐induced increase in [Ca]_in was dependent on external Ca²⁺, was blocked in a dose‐dependent manner by reactive blue 2, and was substantially inhibited by both L‐ and N‐type Ca²⁺ channel blockers. ATP was effective in increasing [Ca]_in in the presence of a desensitizing concentration of nicotine (100 µM), and simultaneous addition of maximal doses of ATP and nicotine caused an additive increase in [Ca]_in, suggesting that ATP acts on a site distinct from nicotinic acetylcholine receptors. ATP also increased the cytosolic Na⁺ concentration as determined by sodium‐binding benzofuran isophthalate microfluorometry. These results suggest that ATP increases Na⁺ influx through P₂ purinoceptor‐associated channels resulting in membrane depolarization, which in turn increases Ca²⁺ influx through voltage‐dependent Ca²⁺ channels. However, ATP still caused a small increase in [Ca]_in under Na⁺‐free conditions, and this [Ca]_in increase was little affected by Ca²⁺ channel blockers. ATP also increased Mn²⁺ influx under Na⁺‐free conditions, as indicated by quenching of fura‐2 fluorescence. These results suggest that nonselective cationic channels activated by ATP are permeable not only to Ca²⁺ but also to Mn²⁺, in addition to monovalent cations.