Inhibition of sodium current by carbamazepine in dorsal root ganglion neurons in vitro.
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Date
2009-04
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Abstract
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 μm), 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 μM 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 μM 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 μM 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.
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Keywords
sodium channel, carbamazepine, sensory neurons, whole cell patch clamp
Citation
Singh Jitendra N, Jain Gaurav, Ramarao Poduri, Sharma Shyam S. Inhibition of sodium current by carbamazepine in dorsal root ganglion neurons in vitro. Indian Journal of Physiology and Pharmacology. 2009 Apr-June; 53(2): 147-154.