Inhibition of sodium current by carbamazepine in dorsal root ganglion neurons in vitro.
Carbamazepine (CBZ), one of the most commonly prescribed antiepileptic drug, is proposed to inhibit Na+ channel. In this study, we have investigated the effects of CBZ on Na+ current, evoked in cultured dorsal root ganglion (DRG) neurons from neonatal rats using whole cell patch clamp technique. In small DRG neurons (20-25 microm), Na+ current was obtained by blocking K+ and Ca2+ currents with appropriate ion replacement and channel blockers. Separation of the Na+ current components was achieved on the basis of response to the conditioning voltage. The CBZ depressed Na+ current in a dose-dependent manner. The maximal Na+ current was depressed at 300 microM of CBZ, where 94 +/- 5.1% of depression was observed. The depression of normalized current amplitude was found to be 72 +/- 13.2%, 84 +/- 10%, 85 +/- 7.1% and 95 +/- 5.2% at 10, 30, 100 and 300 microM of CBZ concentrations, respectively, at -20 mV test pulse, when compared with control. The depression of current amplitude was observed as 48 +/- 12.3%, 42 +/- 15.2%, 71 +/- 17.7% and 90 +/- 5.8% at 10, 30, 100 and 300 microM of CBZ concentration, respectively, at 0 mV voltage pulse. The depression of Na+ currents was found to be dose-dependant at -20 and -10 mV but not at 0 mV, It is concluded that the depression of Na+ currents by CBZ may be responsible for inhibiting the neurotransmitter release.
Singh
Jitendra N
JN
Electrophysiology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S. A. S. Nagar (Mohali) - 160 062. jnsingh@niper.ac.in
Jain
Gaurav
G
Ramarao
Poduri
P
Sharma
Shyam S
SS
D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology*
D000927:Anticonvulsants; D026941:Sodium Channel Blockers; D002220:Carbamazepine; D012964:Sodium