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.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Lecar H,Larsson HP,Grabe Mdoi
10.1016/S0006-3495(03)74708-0subject
Has Abstractpub_date
2003-11-01 00:00:00pages
2854-64issue
5eissn
0006-3495issn
1542-0086pii
S0006-3495(03)74708-0journal_volume
85pub_type
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