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
.