Putative receptor for the cytoplasmic inactivation gate in the Shaker K+ channel

• Published in: Nature (London) 1991-09, Vol.353 (6339), p.86-90
• Main Authors: ISACOFF, E. Y, YUH NUNG, LILY YEH JAN
• Format: Article
• Language: English
• Subjects: Action Potentials; Amino Acid Sequence; Amino acids; Animals; Biochemistry; Biological and medical sciences; Cell Membrane - physiology; Cell physiology; DNA - genetics; Drosophila - genetics; Electric Conductivity; Fundamental and applied biological sciences. Psychology; Inactivation; Ion Channel Gating - physiology; Membrane and intracellular transports; Molecular and cellular biology; Molecular Sequence Data; Mutagenesis, Site-Directed; Mutation; Oocytes - physiology; Potassium Channels - chemistry; Potassium Channels - genetics; Potassium Channels - physiology; Proteins; Transfection; Xenopus
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/353086a0

Inactivation of ion channels is important in the control of membrane excitability. For example, delayed-rectifier K+ channels, which regulate action potential repolarization, are inactivated only slowly, whereas A-type K+ channels, which affect action potential duration and firing frequency, have both fast and slow inactivation. Fast inactivation of Na+ and K+ channels may result from the blocking of the permeation pathway by a positively charged cytoplasmic gate such as the one encoded by the first 20 amino acids of the Shaker B (ShB) K+ channel. We report here that mutation of five highly conserved residues between the proposed membrane-spanning segments S4 and S5 (also termed H4) of ShB affects the stability of the inactivated state and alters channel conductance. One such mutation stabilizes the inactivated state of ShB as well as the inactivated state induced in the delayed-rectifier type K+ channel drk1 by the cytoplasmic application of the ShB N-terminal peptide. The S4-S5 loop, therefore, probably forms part of a receptor for the inactivation gate and lies near the channel's permeation pathway.