Electrostatic Model of S4 Motion in Voltage-Gated Ion Channels

Harold Lecar, H. Peter Larsson, Michael Grabe

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


The S4 transmembrane domain of the family of voltage-gated ion channels is generally thought to be the voltage sensor, whose translocation by an applied electric field produces the gating current. Experiments on hSkMI Na+ channels and both Shaker and EAG K+ channels indicate which S4 residues cross the membrane-solution interface during activation gating. Using this structural information, we derive the steady-state properties of gating-charge transfer for wild-type and mutant Shaker K+ channels. Assuming that the energetics of gating is dominated by electrostatic forces between S4 charges and countercharges on neighboring transmembrane domains, we calculate the total energy as a function of transmembrane displacement and twist of the S4 domain. The resulting electrostatic energy surface exhibits a series of deep energy minima, corresponding to the transition states of the gating process. The steady-state gating-charge distribution is then given by a Boltzmann distribution among the transition states. The resulting gating-charge distributions are compared to experimental results on wild-type and charge-neutralized mutants of the Shaker K+ channel.

Original languageEnglish (US)
Pages (from-to)2854-2864
Number of pages11
JournalBiophysical journal
Issue number5
StatePublished - Nov 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics


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