Mechanism of Voltage Gating in Potassium Channels

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 ho...

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Bibliographic Details
Published in:	Science (American Association for the Advancement of Science) Vol. 336; no. 6078; pp. 229 - 233
Main Authors:	Jensen, Morten Ø., Jogini, Vishwanath, Borhani, David W., Leffler, Abba E., Dror, Ron 0., Shaw, David E.
Format:	Journal Article
Language:	English
Published:	Washington, DC American Association for the Advancement of Science 13-04-2012 The American Association for the Advancement of Science
Subjects:	Animals Biological and medical sciences Cell membranes. Ionic channels. Membrane pores Cell structures and functions Channels Chimeras Crystal structure Deactivation Electric fields Electric potential Fundamental and applied biological sciences. Psychology Hydrophobic and Hydrophilic Interactions Ion Channel Gating Ion channels Ions Kv1.2 Potassium Channel - chemistry Kv1.2 Potassium Channel - metabolism Membrane Potentials Models, Biological Models, Molecular Molecular and cellular biology Molecular Dynamics Simulation Molecular structure Molecules Nerves Neurons Oral rehydration Porosity Potassium Protein Conformation Protein Structure, Secondary Protein Structure, Tertiary Rats Recombinant Fusion Proteins - chemistry Recombinant Fusion Proteins - metabolism Shab Potassium Channels - chemistry Shab Potassium Channels - metabolism Simultaneous interpretation Sodium Voltage Inorganic cation Monovalent cation Voltage-gated canal Simulation Potassium ion Molecular dynamics Ionic channel Mechanism
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0036-8075 1095-9203
DOI:	10.1126/science.1216533