Nerve fiber size-related block of action currents by phenytoin in mammalian nerve.

We investigated nerve fiber size-related actions of phenytoin (PHT) by applying the anticonvulsant on 2-mm-long stretches of desheathed whole nerves, excised from rat sural nerve. Compound action potentials (APs) were elicited by voltage pulses of increasing amplitude and recorded as monophasic action currents of the A alpha beta-type along the surface of the nerve. The area under the action current Q at supramaximal stimulation was reduced by 11 and 30% in solutions containing 10 and 100 microM PHT, respectively, similar to the reduction in peak action current. However, a greater reduction in Q induced by PHT was observed with smaller stimuli at both concentrations. This stimulus-dependent reduction was believed to originate from selective inhibition of the thicker nerve fibers. Using a mathematical model, we separated Q into contributions Q alpha of the alpha-fibers and Q beta of the beta-fibers. In solutions containing 10 microM PHT, Q alpha was reduced by 15% maximally, whereas Q beta was not affected. Both fiber types were reduced < or = 30% in the presence of 100 microM PHT, whereas the relations between Q alpha and Q beta, respectively, and stimulus voltage shifted along the voltage axis for 0.3 V, suggesting that the larger fibers in the A alpha beta-groups were more inhibited by PHT than the smaller ones. Abolition of the early phases of the compound action currents by PHT also indicated loss mainly of faster conducting nerve fibers. We conclude that primarily the larger fibers in the A alpha beta populations were inhibited by the anticonvulsant, strongly suggesting a differential mode of action by PHT on myelinated nerve fibers.