4rue

Publication Abstract from PubMed

Mechanical and thermal activation of ion channels is central to touch, thermosensation, and pain. The TRAAK/TREK K2P 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 K2P4.1 (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 K2P modulation, indicate a means for how the K2P C-terminal cytoplasmic domain affects the C-type gate which lies approximately 40A away, and suggest how lipids and bilayer inner leaflet deformations may gate the channel.

Transmembrane Helix Straightening and Buckling Underlies Activation of Mechanosensitive and Thermosensitive K2P Channels.,Lolicato M, Riegelhaupt PM, Arrigoni C, Clark KA, Minor DL Jr Neuron. 2014 Dec 17;84(6):1198-212. doi: 10.1016/j.neuron.2014.11.017. Epub 2014 , Dec 11. PMID:25500157^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.