MULTIPLE ACTIONS OF NITRIC-OXIDE ON VOLTAGE-DEPENDENT CA2-NEURONS( CHANNELS IN MOUSE CEREBRAL CORTICAL)

We investigated the effects of nitric oxide (NO) on voltage-dependent Ca2+ channels (VDCCs) by examining [Ca-45(2+)]influx into mouse cerebr al cortical neurons. S-nitroso-N-acetylpenicillamine (SNAP) induced a dose-dependent increase in [Ca-45(2+)]influx, which was completely abo lished by hemoglobin, tetrodotoxin and dibucaine. The NO-induced [Ca-4 5(2+)]influx was significantly inhibited by verapamil and omega-agatox in VIA(omega-AGX), whereas omega-conotoxin GVIA(omega-CTX) had no effe cts 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-in duced [Ca-45(2+)]influx by about 40, 26 and 34%, respectively, indicat ing 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 pr esence 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 abolis hed the influx. These results indicate that NO induces [Ca-45(2+)] inf lux via the opening of L- and P-typed VDCCs subsequent to neuronal mem brane depolarization and that NO itself inhibited the function of N-ty ped VDCC in the cerebral cortical neurons. (C) 1998 Elsevier Science B .V.