Electrostatic model of S4 motion in voltage-gated ion channels.
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.
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA. hlecar@uclink4.berkley.edu
Harold
H
Lecar
H Peter
HP
Larsson
Michael
M
Grabe
D000595:Amino Acid Sequence; D003198:Computer Simulation; D004735:Energy Transfer; D015640:Ion Channel Gating; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D015221:Potassium Channels / Q000737:chemistry*; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry*; D011487:Protein Conformation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D051637:Shaker Superfamily of Potassium Channels; D055672:Static Electricity; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C088750:S4 peptide, Drosophila Shaker potassium channel; D051637:Shaker Superfamily of Potassium Channels