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.
Patton
D E
DE
Department of Microbiology and Molecular Genetics, University of California, Irvine 92717.
West
J W
JW
Catterall
W A
WA
Goldin
A L
AL
D000595:Amino Acid Sequence; D001483:Base Sequence; D002678:Chimera; D015640:Ion Channel Gating / Q000502:physiology*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology*; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*
D015345:Oligonucleotide Probes; D010446:Peptide Fragments; D015221:Potassium Channels; D015222:Sodium Channels