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 whol e nerves, excised from rat sural nerve. Compound action potentials (AP s) were elicited by voltage pulses of increasing amplitude and recorde d as monophasic action currents of the A alpha beta-type along the sur face 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 mu M PHT, respectively, similar to the reduction in peak action cu rrent. However, a greater reduction in Q induced by PHT was observed w ith smaller stimuli at both concentrations. This stimulus-dependent re duction was believed to originate from selective inhibition of the thi cker nerve fibers. Using a mathematical model, we separated Q into con tributions Q(alpha) of the alpha-fibers and Q(beta) of the beta-fibers . In solutions containing 10 mu M PHT, Q(alpha) was reduced by 15% max imally, whereas Q(beta) was not affected. Both fiber types were reduce d less than or equal to 30% in the presence of 100 mu M PHT, whereas t he 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 th an the smaller ones. Abolition of the early phases of the compound act ion currents by PHT also indicated loss mainly of faster conducting ne rve fibers. We conclude that primarily the larger fibers in the A alph a beta populations were inhibited by the anticonvulsant, strongly sugg esting a differential mode of action by PHT on myelinated nerve fibers .