Multiple actions of nitric oxide on voltage-dependent Ca2+ channels in mouse cerebral cortical neurons

We investigated the effects of nitric oxide (NO) on voltage-dependent Ca2+ channels (VDCCs) by examining [Ca-45(2+)]influx into mouse cerebral cortical neurons. S-nitroso-N-acetylpenicillamine (SNAP) induced a dose-dependent increase in [Ca-45(2+)]influx, which was completely abolished by hemoglobin, tetrodotoxin and dibucaine. The NO-induced [Ca-45(2+)]influx was significantly inhibited by verapamil and omega-agatoxin VIA(omega-AGX), whereas omega-conotoxin GVIA(omega-CTX) had no effects on the NO-induced [Ca-45(2+)]influx. KCl (30 mM) stimulated [Ca-45(2+)]influx, and verapamil, omega-CTX and omega-AGX reduced the KCl-induced [Ca-45(2+)]influx by about 40, 26 and 34%, respectively, indicating that the neurons used here possess L-, N- and P-typed VDCCs. SNAP itself reduced KCl-induced [Ca-45(2+)]influx by about 28.5%. In the presence of both KCl and SNAP, omega-CTX showed no effects on the influx, while verapamil and omega-AGX significantly inhibited the influx and the concomitant presence of verapamil and omega-AGX completely abolished the influx. These results indicate that NO induces [Ca-45(2+)] influx via the opening of L- and P-typed VDCCs subsequent to neuronal membrane depolarization and that NO itself inhibited the function of N-typed VDCC in the cerebral cortical neurons. (C) 1998 Elsevier Science B.V.