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Science. 2012 Apr 13;336(6078):229-33. doi: 10.1126/science.1216533.

Mechanism of voltage gating in potassium channels.

Author information

1
D E Shaw Research, New York, NY 10036, USA. morten.jensen@DEShawResearch.com

Abstract

The mechanism of ion channel voltage gating-how channels open and close in response to voltage changes-has been debated since Hodgkin and Huxley's seminal discovery that the crux of nerve conduction is ion flow across cellular membranes. Using all-atom molecular dynamics simulations, we show how a voltage-gated potassium channel (KV) switches between activated and deactivated states. On deactivation, pore hydrophobic collapse rapidly halts ion flow. Subsequent voltage-sensing domain (VSD) relaxation, including inward, 15-angstrom S4-helix motion, completes the transition. On activation, outward S4 motion tightens the VSD-pore linker, perturbing linker-S6-helix packing. Fluctuations allow water, then potassium ions, to reenter the pore; linker-S6 repacking stabilizes the open pore. We propose a mechanistic model for the sodium/potassium/calcium voltage-gated ion channel superfamily that reconciles apparently conflicting experimental data.

PMID:
22499946
DOI:
10.1126/science.1216533
[Indexed for MEDLINE]
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