Channelpedia

The pore of voltage-gated potassium ion channels is strained when closed.


Authors: Philip W Fowler, Mark S P Sansom

Journal, date & volume: Nat Commun, 2013 , 4, 1872

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23695666

Channelpedia reference in: Kv2.1

Abstract
Voltage-gated potassium channels form potassium-selective pores in cell membranes. They open or close in response to changes in the transmembrane potential and are essential for generating action potentials, and thus for the functioning of heart and brain. While a mechanism for how these channels close has been proposed, it is not clear what drives their opening. Here we use free energy molecular dynamics simulations to show that work must be done on the pore to reduce the kink in the pore-lining (S6) α-helices, thereby forming the helix bundle crossing and closing the channel. Strain is built up as the pore closes, which subsequently drives opening. We also determine the effect of mutating the PVPV motif that causes the kink in the S6 helix. Finally, an approximate upper limit on how far the S4 helix is displaced as the pore closes is estimated.