European Biophysics Journal

, Volume 41, Issue 9, pp 705–721 | Cite as

The sliding-helix voltage sensor: mesoscale views of a robust structure–function relationship

  • Alexander PeyserEmail author
  • Wolfgang Nonner
Original Paper


The voltage sensor (VS) domain of voltage-gated ion channels underlies the electrical excitability of living cells. We simulate a mesoscale model of the VS domain to determine the functional consequences of some of its physical elements. Our mesoscale model is based on VS charges, linear dielectrics, and whole-body motion, applied to an S4 “sliding helix.” The electrostatics under voltage-clamped boundary conditions are solved consistently using a boundary-element method. Based on electrostatic configurational energy, statistical-mechanical expectations of the experimentally observable relation between displaced charge and membrane voltage are predicted. Consequences of the model are investigated for variations of S4 configuration (α- and 310-helical), countercharge alignment with S4 charges, protein polarizability, geometry of the gating canal, screening of S4 charges by the baths, and fixed charges located at the bath interfaces. The sliding-helix VS domain has an inherent electrostatic stability in the explored parameter space: countercharges present in the region of weak dielectric always retain an equivalent S4 charge in that region but allow sliding movements displacing 3–4 e 0. That movement is sensitive to small energy variations (<2 kT) along the path dependent on a number of electrostatic parameters tested in our simulations. These simulations show how the slope of the relation between displaced charge and voltage could be tuned in a channel.


Ion channels Computer simulation Potassium channels Voltage gated Voltage sensor domain 



The authors are grateful for the support of the National Institutes of Health (grant GM083161) to W.N. and a Graduate Research Fellowship of the National Science Foundation to A.P. We thank Drs. Alice Holohean, Peter Larsson, and Karl Magleby for helpful discussions.

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Copyright information

© European Biophysical Societies' Association 2012

Authors and Affiliations

  1. 1.Department of Physiology and BiophysicsUniversity of Miami Computational Biophysics, German Research School for Simulation SciencesJülichGermany
  2. 2.Department of Physiology and BiophysicsUniversity of MiamiMiamiUSA

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