A PEPTIDE SEGMENT CRITICAL FOR SODIUM-CHANNEL INACTIVATION FUNCTIONS AS AN INACTIVATION GATE IN A POTASSIUM CHANNEL

The short cytoplasmic peptide segment connecting domains III and IV of voltage-gated sodium channels (III-IV linker) is essential for fast i nactivation. To test the functional similarity between the III-IV link er and the potassium channel inactivation particle, we attached the II I-IV linker to the amino terminus of a noninactivating potassium chann el. This chimeric channel inactivated rapidly and displayed biophysica l properties similar to Shaker A-type potassium channels. Recovery f r om inactivation in the chimeric channels was accelerated by high exter nal potassium, consistent with the idea that potassium ions passing th rough the channel displaced the III-IV linker inactivation particle. A mutation that completely abolishes fast inactivation in rat brain sod ium channels also completely abolished inactivation in the chimera. Th ese results demonstrate that the sodium channel III-IV linker can func tion as a fast inactivation gate and suggest a functional relationship between the fast inactivation processes of sodium and potassium chann els.