Proline mutations on the S4 segment of rat brain sodium channel II.

We have studied S4-proline mutants of the rat brain sodium channel II. In mutant A224P one proline was added on the S4 segment of repeat I, and in mutant P1313V a proline was removed from the segment S4 of the repeat II. In both mutants, the activation curve was shifted to more positive potentials, without changing the steepness of the voltage dependence. The time course of inactivation, consisting of two exponential components, was similar in the wild type and in mutant A224P. Differently, the decay of the current in mutant P1313V had only one component, with a time constant similar to that of the fast component of wild type channels. This change in kinetics was accompanied in mutant P1313V by a change in the voltage dependence of the apparent steady-state inactivation. We conclude that the addition or deletion of prolines in segment S4 does not affect significantly the activation of sodium channels, but alters their mode of inactivation.