Characterization in Inhibitory Effectiveness of Carbamazepine in Voltage-Gated Na + and Erg-Mediated K + Currents in a Mouse Neural Crest-Derived (Neuro-2a) Cell Line.

Carbamazepine (CBZ, Tegretol ® ) is an anticonvulsant used in the treatment of epilepsy and neuropathic pain; however, several unwanted effects of this drug have been noticed. Therefore, the regulatory actions of CBZ on ionic currents in electrically excitable cells need to be reappraised, although its efficacy in suppressing voltage-gated Na + current ( I Na ) has been disclosed. This study was undertaken to explore the modifications produced by CBZ on ionic currents (e.g., I Na and erg -mediated K + current [ I K(erg) ]) measured from Neuro-2a (N2a) cells. In these cells, we found that this drug differentially suppressed the peak (transient, I Na(T) ) and sustained (late, I Na(L) ) components of I Na in a concentration-dependent manner with effective IC 50 of 56 and 18 μM, respectively. The overall current-voltage relationship of I Na(T) with or without the addition of CBZ remained unchanged; however, the strength (i.e., ∆area) in the window component of I Na ( I Na(W) ) evoked by the short ascending ramp pulse (V ramp ) was overly lessened in the CBZ presence. Tefluthrin (Tef), a synthetic pyrethroid, known to stimulate I Na , augmented the strength of the voltage-dependent hysteresis (Hys (V) ) of persistent I Na ( I Na(P) ) in response to the isosceles-triangular V ramp ; moreover, further application of CBZ attenuated Tef-mediated accentuation of I Na(P) 's Hys (V) . With a two-step voltage protocol, the recovery of I Na(T) inactivation seen in Neuro-2a cells became progressively slowed by adding CBZ; however, the cumulative inhibition of I Na(T) evoked by pulse train stimulation was enhanced during exposure to this drug. Neuro-2a-cell exposure to CBZ (100 μM), the magnitude of erg -mediated K + current measured throughout the entire voltage-clamp steps applied was mildly inhibited. The docking results regarding the interaction of CBZ and voltage-gate Na + (Na V ) channel predicted the ability of CBZ to bind to some amino-acid residues in Na V due to the existence of a hydrogen bond or hydrophobic contact. It is conceivable from the current investigations that the I Na ( I Na(T) , I Na(L) , I Na(W) , and I Na(P) ) residing in Neuro-2a cells are susceptible to being suppressed by CBZ, and that its block on I Na(L) is larger than that on I Na(T) . Collectively, the magnitude and gating of Na V channels produced by the CBZ presence might have an impact on its anticonvulsant and analgesic effects occurring in vivo.