Differential block of two types of sodium channels by anticonvulsants

THE differential effects of the anticonvulsants phenytoin and carbamazepine on the sodium channels of rat dorsal root ganglion (DRG) neurons were studied using the patch clamp technique. The action potentials from tetrodotoxin-resistant (TTX-R) cells were less sensitive to phenytoin and carbamazepine than those from tetrodotoxin-sensitive (TTX-S) cells. The steady-state inactivation curve for TTX-S sodium channels was shifted by as much as 20.6 mV and 11.4 mV by phenytoin and carbamazepine at 300 μM, respectively, yet the curve for TTX-R sodium channels was shifted only by 6.0 mV and 6.9 mV, respectively. Thus, the differential action potential block of TTX-S and TTX-R cells by phenytoin and carbamazepine is due to different voltage dependence of and differential drug effects on the inactivation kinetics of two types of sodium channels.