Phenobarbital induces slow recovery from sodium inactivation at the nodal membrane

Voltage-clamp experiments were performed on single myelinated nerve fibres of Rana esculenta at 20 degrees C in Ringer's solution and in solutions containing phenobarbital-sodium ([PB] less than or equal to 5 mM). The reduction of the sodium current under phenobarbital could be explained by an increase in the resting sodium inactivation; h infinity (E) was shifted towards more negative membrane potentials. The recovery from sodium inactivation proceeded with two time constants. The fast process could be described with the same time constant as in Ringer's solution, whereas the slow process had a time constant approx. 40 times larger. The slow process was also potential-dependent and could be described by 1/(0.025 alpha h + beta h), where alpha h and beta h denoted the rate constants in Ringer's solution. With the measured blockage of sodium channels by phenobarbital, both the shift of h infinity (E) and the slow recovery from sodium inactivation could be explained.