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 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 microM), 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.
Sorimachi
M
M
Department of Physiology, Kagoshima University School of Medicine, Japan.
Abe
Y
Y
Furukawa
K
K
Akaike
N
N
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002642:Chick Embryo; D003600:Cytosol / Q000378:metabolism; D005711:Gallopamil / Q000494:pharmacology; D005726:Ganglia, Parasympathetic / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D009538:Nicotine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology; D011983:Receptors, Purinergic / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D020866:omega-Conotoxin GVIA
D010455:Peptides; D011687:Purines; D011978:Receptors, Nicotinic; D011983:Receptors, Purinergic; D005711:Gallopamil; D009538:Nicotine; D000255:Adenosine Triphosphate; D020866:omega-Conotoxin GVIA; D012964:Sodium; D009543:Nifedipine; D011188:Potassium; D002118:Calcium