Voltage-sensing arginines in a potassium channel permeate and occlude cation-selective pores

  • Tombola F
  • Pathak M
  • Isacoff E
  • 87

    Readers

    Mendeley users who have this article in their library.
  • 178

    Citations

    Citations of this article.

Abstract

Voltage-gated ion channels sense voltage by shuttling arginine residues located in the S4 segment across the membrane electric field. The molecular pathway for this arginine permeation is not understood, nor is the filtering mechanism that permits passage of charged arginines but excludes solution ions. We find that substituting the first S4 arginine with smaller amino acids opens a high-conductance pathway for solution cations in the Shaker K+channel at rest. The cationic current does not flow through the central K+pore and is influenced by mutation of a conserved residue in S2, suggesting that it flows through a protein pathway within the voltage-sensing domain. The current can be carried by guanidinium ions, suggesting that this is the pathway for transmembrane arginine permeation. We propose that when S4 moves it ratchets between conformations in which one arginine after another occupies and occludes to ions the narrowest part of this pathway.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Francesco Tombola

  • Medha M. Pathak

  • Ehud Y. Isacoff

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free