Department of Anesthesiology

You are here

Transmembrane helix straightening and buckling underlies activation of mechanosensitive and thermosensitive K(2P) channels.

TitleTransmembrane helix straightening and buckling underlies activation of mechanosensitive and thermosensitive K(2P) channels.
Publication TypeJournal Article
Year of Publication2014
AuthorsLolicato M, Riegelhaupt PM, Arrigoni C, Clark KA, Minor DL
JournalNeuron
Volume84
Issue6
Pagination1198-212
Date Published2014 Dec 17
ISSN1097-4199
KeywordsAnimals, Cell Membrane, Cells, Cultured, Ion Channel Gating, Lipid Bilayers, Mutation, Oocytes, Physical Stimulation, Potassium Channels, Protein Structure, Secondary, Temperature, Xenopus laevis
Abstract

Mechanical and thermal activation of ion channels is central to touch, thermosensation, and pain. The TRAAK/TREK K(2P) potassium channel subfamily produces background currents that alter neuronal excitability in response to pressure, temperature, signaling lipids, and anesthetics. How such diverse stimuli control channel function is unclear. Here we report structures of K(2P)4.1 (TRAAK) bearing C-type gate-activating mutations that reveal a tilting and straightening of the M4 inner transmembrane helix and a buckling of the M2 transmembrane helix. These conformational changes move M4 in a direction opposite to that in classical potassium channel activation mechanisms and open a passage lateral to the pore that faces the lipid bilayer inner leaflet. Together, our findings uncover a unique aspect of K(2P) modulation, indicate a means for how the K(2P) C-terminal cytoplasmic domain affects the C-type gate which lies ∼40Å away, and suggest how lipids and bilayer inner leaflet deformations may gate the channel.

DOI10.1016/j.neuron.2014.11.017
Alternate JournalNeuron
PubMed ID25500157
PubMed Central IDPMC4270892
Grant ListR01 MH093603 / MH / NIMH NIH HHS / United States
R01-MH093603 / MH / NIMH NIH HHS / United States