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 of 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.

Stefani, A., Pisani, A., De Murtas, M., Mercuri, N., Marciani, M., & Calabresi, P. (1995). Action of GP 47779, the active metabolite of oxcarbazepine, on the corticostriatal system. II. Modulation of high-voltage-activated calcium currents. EPILEPSIA, 36(10), 997-1002.

Action of GP 47779, the active metabolite of oxcarbazepine, on the corticostriatal system. II. Modulation of high-voltage-activated calcium currents

STEFANI, ALESSANDRO;PISANI, ANTONIO;MERCURI, NICOLA BIAGIO;MARCIANI, MARIA GRAZIA;CALABRESI, PAOLO
1995-10

Abstract

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 of 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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/26 - Neurologia
English
Con Impact Factor ISI
Animals; Receptors, Presynaptic; Corpus Striatum; Cell Separation; Nifedipine; Dihydropyridines; Rats; Calcium Channels; Cerebral Cortex; Patch-Clamp Techniques; Carbamazepine; Neural Pathways; Rats, Wistar; Glutamates; Synaptic Transmission; Anticonvulsants; Male
Stefani, A., Pisani, A., De Murtas, M., Mercuri, N., Marciani, M., & Calabresi, P. (1995). Action of GP 47779, the active metabolite of oxcarbazepine, on the corticostriatal system. II. Modulation of high-voltage-activated calcium currents. EPILEPSIA, 36(10), 997-1002.
Stefani, A; Pisani, A; De Murtas, M; Mercuri, Nb; Marciani, Mg; Calabresi, P
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/88320
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