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 inactivation. To test the functional similarity between the III-IV linker and the potassium channel inactivation particle, we attached the III-IV linker to the amino terminus of a noninactivating potassium channel. This chimeric channel inactivated rapidly and displayed biophysical properties similar to Shaker A-type potassium channels. Recovery from inactivation in the chimeric channels was accelerated by high external potassium, consistent with the idea that potassium ions passing through the channel displaced the III-IV linker inactivation particle. A mutation that completely abolishes fast inactivation in rat brain sodium channels also completely abolished inactivation in the chimera. These results demonstrate that the sodium channel III-IV linker can function as a fast inactivation gate and suggest a functional relationship between the fast inactivation processes of sodium and potassium channels.