Effects of diphenylhydantoin and phenobarbital on voltage-clamped myelinated nerve.

Diphenylhydantoin (DPH) and phenobarbital (PB) have a selective action in blocking spontaneous activity in nerves made hyperexcitable by lowering the calcium concentration of the bathing medium (Rosenberg, P. and Bartels, E. 1967 J. Pharmacol. Exp. Ther. 155, 532-544.). To investigate this further, we examined the action of DPH and PB on voltage-clamped single myelinated nerves at two different calcium concentrations. In 1.8 mM calcium Ringer, DPH reduced the sodium permeability (PNa) without affecting the potassium conductance (GK) or the voltage-dependent time constants of sodium activation (taum) and inactivation (tauh), and potassium activation (taun). PB was similar to DPH except that in addition to reducing PNa, it shifted taum in the direction of depolarization. When the calcium concentration was lowered to 0.36 mM, the curves relating taum and taun to membrane potential were shifted in the direction of hyperpolarization, as expected. However, the addition of DPH or PB reduced or abolished these shifts. It is suggested that both DPH and PB stabilize hyperexcitable membranes by an action on the parameter m, and that this may contribute to their antiepileptic action.