MECHANISM UNDERLYING THE ATP-INDUCED INCREASE IN THE CYTOSOLIC CA2+ CONCENTRATION IN CHICK CILIARY GANGLION NEURONS

We examined the mechanism underlying the ATP-induced increase in the c ytosolic Ca2+ concentration ([Ca](in)) in acutely isolated chick cilia ry ganglion neurons, using fura-2 microfluorometry. The ATP-induced in crease in [Ca](in) was dependent on external Ca2+, was blocked in a do se-dependent manner by reactive blue 2, and was substantially inhibite d by both L- and N-type Ca2+ channel blockers. ATP was effective in in creasing [Ca](in) in the presence of a desensitizing concentration of nicotine (100 mu M), 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. A TP also increased the cytosolic Na+ concentration as determined by sod ium-binding benzofuran isophthalate microfluorometry. These results su ggest that ATP increases Na+ influx through P-2 purinoceptor-associate d channels resulting in membrane depolarization, which in turn increas es Ca2+ influx through voltage-dependent Ca2+ channels. However, ATP s till caused a small increase in [Ca](in) under Na+-free conditions, an d this [Ca](in) increase was little affected by Ca2+ channel blockers. ATP also increased Mn2+ influx under Na+-free conditions, as indicate d by quenching of fura-2 fluorescence. These results suggest that nons elective cationic channels activated by ATP are permeable not only to Ca2+ but also to Mn2+, in addition to monovalent cations.