From the gating charge response to pore domain movement: Initial motions of Kv1.2 dynamics under physiological voltage changes

Elizabeth J. Denning, Paul S. Crozier, Jonathan N. Sachs, Thomas B. Woolf

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Recent structures of the potassium channel provide an essential beginning point for explaining how the pore is gated between open and closed conformations by changes in membrane voltage. Yet, the molecular details of this process and the connections to transmembrane gradients are not understood. To begin addressing how changes within a membrane environment lead to the channel's ability to sense shifts in membrane voltage and to gate, we performed double-bilayer simulations of the Kv1.2 channel. These double-bilayer simulations enable us to simulate realistic voltage drops from resting potential conditions to depolarized conditions by changes in the bath conditions on each side of the bilayer. Our results show how the voltage sensor domain movement responds to differences in transmembrane potential. The initial voltage sensor domain movement, S4 in particular, is modulated by the gating charge response to changes in voltage and is initially stabilized by the lipid headgroups. We show this response is directly coupled to the initial stages of pore domain motion. Results presented here provide a molecular model for how the pre-gating process occurs in sequential steps: Gating charge response, movement and stabilization of the S4 voltage sensor domain, and movement near the base of the S5 region to close the pore domain.

Original languageEnglish (US)
Pages (from-to)397-421
Number of pages25
JournalMolecular Membrane Biology
Issue number8
StatePublished - Dec 2009

Bibliographical note

Funding Information:
The authors thank Oliver Beckstein and Naveen Michaud-Agrawal for valuable discussions and contributions to MDAnalysis. This research was funded by a grant from National Institutes of Health (GM064746). Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.


  • Double-layer effect
  • Ionic solution
  • S4 domain
  • Voltage gating


Dive into the research topics of 'From the gating charge response to pore domain movement: Initial motions of Kv1.2 dynamics under physiological voltage changes'. Together they form a unique fingerprint.

Cite this