Phenytoin and carbamazepine: Differential inhibition of sodium currents in small cells from adult rat dorsal root ganglia

We determined the effects of carbamazepine and phenytoin, anticonvulsant drugs used to treat neuropathic pain, on the heterogeneous population of Na+ channels in patch-clamped small cells from adult rat dorsal root ganglia. Both fast tetrodotoxin-sensitive (ITX-S) and slow TTX-resistant (TTX-R) currents were inhibited by 10-100 mu M drug. TTX-R currents were divided into two classes. Control type I currents had a very depolarized voltage for 50% availability (V-h) of ca. -29 mV and 17% reduction in current by the 20th pulse at 1 Hz. Control type II currents had a V-h closer to -46 mV and 49% reduction in current at 1 Hz. At 0.1 Hz, which gave relatively little loss of control current, 100 mu M drug caused 53 +/- 4% (n = 5) block of type I current and 88 +/- 2% inhibition of type II current (n = 4). Strong 1 s hyperpolarizing prepulses relieved most of the fast channel block but had much less effect on blocked TTX-R channels. (C) 1997 Elsevier Science Ireland Ltd.