Gating charge displacement in voltage-gated ion channels involves limited transmembrane movement

Nature. 2005 Aug 11;436(7052):852-6. doi: 10.1038/nature03888.

Abstract

Voltage-gated ion channels are responsible for generating electrical impulses in nerves and other excitable cells. The fourth transmembrane helix (S4) in voltage-gated channels is the primary voltage-sensing unit that mediates the response to a changing membrane electric field. The molecular mechanism of voltage sensing, particularly with respect to the magnitude of the transmembrane movement of S4, remains controversial. To determine the extent of this transmembrane movement, we use fluorescent resonance energy transfer between the S4 domain and a reference point in the lipid bilayer. The lipophilic ion dipicrylamine distributes on either side of the lipid bilayer depending on the membrane potential, and is used here as a resonance-energy-transfer acceptor from donor molecules attached to several positions in the Shaker K+ channel. A voltage-driven transmembrane movement of the donor should produce a transient fluorescence change because the acceptor also translocates as a function of voltage. In Shaker K+ channels no such transient fluorescence is observed, indicating that the S4 segment does not translocate across the lipid bilayer. Based on these observations, we propose a molecular model of voltage gating that can account for the observed 13e gating charge with limited transmembrane S4 movement.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Membrane / metabolism*
  • Fluorescence Resonance Energy Transfer
  • Ion Channel Gating*
  • Lipid Bilayers / metabolism
  • Membrane Potentials
  • Models, Molecular
  • Molecular Probes
  • Movement*
  • Picrates
  • Potassium Channels / chemistry
  • Potassium Channels / genetics
  • Potassium Channels / metabolism
  • Potassium Channels, Voltage-Gated / chemistry
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism*
  • Protein Conformation
  • Shaker Superfamily of Potassium Channels

Substances

  • Lipid Bilayers
  • Molecular Probes
  • Picrates
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Shaker Superfamily of Potassium Channels
  • dipicrylamine