ACTION OF GP-47779, THE ACTIVE METABOLITE OF OXCARBAZEPINE, ON THE CORTICOSTRIATAL SYSTEM .2. MODULATION OF HIGH-VOLTAGE-ACTIVATED CALCIUM CURRENTS

GP 47779, the active metabolite of oxcarbazepine (OCBZ) inhibits glutamatergic excitatory postsynaptic potentials (EPSPs) in rat striatum (described in the accompanying article). This effect was presumed to involve the modulation of the calcium (Ca2+) signals at either pre- or postsynaptic level. Therefore, we directly tested whether GP 47779 could modulate Ca2+ conductances in cortical as well as in striatal neurons. GP 47779 produced a reversible dose-dependent decrease in high-voltage-activated (HVA) Ca2+ currents evoked by membrane depolarization in isolated cortical pyramidal cells. GP 47779-mediated reduction in HVA Ca2+ currents, if occurring also at corticostriatal axon terminals, might explain the reduction of glutamate release in the striatum. An inhibitory action of GP 47779 on HVA Ca2+ currents was also observed in isolated striatal neurons. The effect on HVA Ca2+ currents in cortical and striatal neurons persisted in the presence of nifedipine, suggesting that dihydropyridine-sensitive channels were not involved in the GP 47779-mediated responses. We propose that the modulation of HVA Ca2+ channels by this carbamazepine (CBZ) analogue may account for its inhibitory action on transmitter release.