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 p ositive potentials, without changing the steepness of the voltage depe ndence. The time course of inactivation, consisting of two exponential components, was similar in the wild type and in mutant A224P. Differe ntly, 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 t ype channels. This change in kinetics was accompanied in mutant P1313V by a change in the voltage dependence of the apparent steady-state in activation. We conclude that the addition or deletion of prolines in s egment S4 does not affect significantly the activation of sodium chann els, but alters their mode of inactivation. (C) 1994 Academic Press, I nc.