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  • Title: Electrostatic model of S4 motion in voltage-gated ion channels.
    Author: Lecar H, Larsson HP, Grabe M.
    Journal: Biophys J; 2003 Nov; 85(5):2854-64. PubMed ID: 14581190.
    Abstract:
    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.
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