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Mechanism of Voltage Gating in Potassium Channels
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Journal Article
Mechanism of Voltage Gating in Potassium Channels
2012
Overview
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/caldum voltage-gated ion channel superfamily that reconciles apparently conflicting experimental data.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Biological and medical sciences
/ calcium
/ cations
/ Cell membranes. Ionic channels. Membrane pores
/ Cell structures and functions
/ Channels
/ Chimeras
/ Fundamental and applied biological sciences. Psychology
/ Hydrophobic and Hydrophilic Interactions
/ Ions
/ Kv1.2 Potassium Channel - chemistry
/ Kv1.2 Potassium Channel - metabolism
/ Molecular and cellular biology
/ Molecular Dynamics Simulation
/ Nerves
/ Neurons
/ Porosity
/ Protein Structure, Secondary
/ Rats
/ Recombinant Fusion Proteins - chemistry
/ Recombinant Fusion Proteins - metabolism
/ Shab Potassium Channels - chemistry
/ Shab Potassium Channels - metabolism
/ Sodium
/ Voltage
