Molecular mechanism of allosteric modification of voltage-dependent sodium channels by local anesthetics.

ABSTRACT: The hallmark of many intracellular pore blockers such as tetra-alkylammonium compounds and local anesthetics is their ability to allosterically modify the movement of the voltage sensors in voltage-dependent ion channels. For instance, the voltage sensor of domain III is specifically stabilized in the activated state when sodium currents are blocked by local anesthetics. The molecular mechanism underlying this long-range interaction between the blocker-binding site in the pore and voltage sensors remains poorly understood. Here, using scanning mutagenesis in combination with voltage clamp fluorimetry, we systematically evaluate the role of the internal gating interface of domain III of the sodium channel. We find that several mutations in the S4-S5 linker and S5 and S6 helices dramatically

SUBMITTER: Arcisio-Miranda M 

PROVIDER: S-EPMC2964522 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature