Peroxynitrite affects Ca2+ influx through voltage-dependent calcium channels

The effect of peroxynitrite (OONO-) on voltage-dependent Ca2+ channels (VDCCs) was examined by measuring [Ca-45(2+)] influx into mouse cerebral cortical neurones. OONO- time- and dose-dependently increased [Ca-45(2+)] influx and this increase was abolished by manganese (III) tetrakis (4-benzoic acid) porphyrin, a scavenger for OONO-. Inhibition of cyclic GMP (cGMP) formation did not alter the OONO--induced [Ca-45(2+)] influx. OONO-, as well as 30 mM KCI, significantly increased fluorescence intensity of cell-associated bis-(1,3-dibutylbarbituric acid) trimethine oxonol (bis-oxonol). Tetrodotoxin and membrane stabilizers such as lidocaine dose-dependently suppressed OONO--induced [Ca-45(2+)] influx. Although each of 1 muM nifedipine and 1 muM omega -agatoxin VIA (omega -ATX) significantly inhibited the OONO--induced [Ca-45(2+)] influx and the concomitant presence of these agents completely abolished the influx, 1 muM omega -conotoxin GVIA (omega -CTX) showed no effect on the influx. On the other hand, OONO- itself reduced 30 mM KCI-induced [Ca-45(2+)] influx to the level of [Ca-45(2+) influx induced by OONO- atone, and the magnitude of this reduction was as same as that of KCI-induced [Ca-45(2+)] influx by w-CTX. These results indicate that OONO- increases [Ca-45(2+)] influx into the neurones through opening P/Q- and L-type VDCCs subsequent to depolarization, and inhibits the influx through N-type VDCCs.