Diphenylhydantoin reduces veratridine-induced sodium permeability in frog skeletal muscle

The effect of the anti-epileptic drug 5,5'-diphenylhydantoin (Dilantin) on Na permeability (PNa) in frog skeletal muscle was studied. Because there is no detectable tetrodotoxin-sensitive Na permeability in resting frog muscle, PNa was induced using the alkaloid 'neurotoxin' veratridine. Veratridine has been previously characterized as a useful 'tool' for producing a population of open Na channels in frog muscle. The amount of sodium permeability produced by veratridine was quantified in two ways: by measuring (a) membrane potential (Vm) and (b) 22Na influx. Dilantin was shown to reverse veratridine-induced depolarization by approximately one-third and to inhibit veratridine-induced Na influx in a dose-dependent manner, with an apparent Km of 78 +/- 8 microM.