Mechanisms for peroxynitrite-induced Ca2+ influx into mouse cerebral cortical neurons *
Effect of peroxynitrile (OONO-) on voltage-dependent Ca2+ channels (VDCCs) was examined by measuring [45Ca2+] influx into mouse cerebral cortical neurons. OONO- increased [45Ca2+] influx in time-and dose-dependent manners. Cyclic GMP formation did not alter the OONO--induced [45Ca2+] influx. Tetrodotoxin and membrane stabilizers such as lidocaine and dibucaine dosc-dependently suppressed the OONO--induｃed [45Ca2+] influx. Each of nifedipine and ω-agatoxin VIA (ω-ATX) significantly inhibited the OONO--induced [45Ca2+] influx and concomitant presence of these agents completely abolished the influx, while ω-ccmotoxm GVIA (ω-CTX) showed no effects on the influx. On the other hand, OONO- itself significantly decreased 30 mM KCl-induced [45Ca2+] influx to the level of [45Ca2+] influx induced by OONO- alone and to the level of KCl-induced [45Ca2+] influx determined in ihe presence of ω-CTX. In addition, the influx by both KC1 and OONO- disappeared by in the concomitant presence of nifedipine and ω-ATX, These results indicate that OONO- increases [45Ca2+] influx into neurons through opening P/Q-and L-typed VDCCs subsequent to depolarization of neuronal membrane and that has an inhibitory action on N-typed VDCC. (Accepted on September 30, 1998) Kawasaki Igakkaishi 24(3) : 149-159. 1998
