Receptor-mediated calcium influx in PC12 cells. ATP and bradykinin activate two independent pathways.
In the neurosecretory cell line PC12 the cytosolic free Ca2+ concentration, [Ca2+]i, and membrane potential were affected by both external ATP and the nonapeptide bradykinin, BK. The latter caused a rapid and large release of Ca2+ from intracellular stores (Ca2+ redistribution) and, in the presence of external Ca2+, a long lasting, but moderate Ca2+ influx, which was insensitive to dihydropyridine blockers. On the contrary, ATP evoked a [Ca2+]i rise which rapidly inactivated. At least three different mechanisms accounted for the ATP-induced increase in [Ca2+]i: less than 20% of the total response was due to intracellular Ca2+ redistribution, consistent with a small increase in inositol 1,4,5-trisphosphate level; the rest (over 80%) was equally accounted for by ATP-activated cation channels and voltage-gated Ca2+ channels. ATP and BK (the latter after K+ channel blockade) caused plasma membrane depolarization. With both agonists the inward current was carried by both Na+ and Ca2+, although the BK-activated current appeared to be more selective for Ca2+. Channels triggered by ATP and BK differed not only in their cation selectivity, but also in modulation by both [Ca2+]i and drugs such as the phorbol ester phorbol 12-myristate 13-acetate and the new antagonist of ligand-activated Ca2+ influx, SK&F 96365.
Fasolato
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Institute of General Pathology, Consiglio Nazionale delle Richerche Center of Biomembranes, University of Padova, Italy.
Pizzo
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Pozzan
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D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000310:Adrenal Gland Neoplasms; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D004533:Egtazic Acid / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D010673:Pheochromocytoma; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats
D007093:Imidazoles; D010975:Platelet Aggregation Inhibitors; D004533:Egtazic Acid; D000255:Adenosine Triphosphate; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D001920:Bradykinin; D002118:Calcium