title: Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K+ channels.
abstract: Mechanosensitive ion channels underlie neuronal responses to physical forces in the sensation of touch, hearing, and other mechanical stimuli. The fundamental basis of force transduction in eukaryotic mechanosensitive ion channels is unknown. Are mechanical forces transmitted directly from membrane to channel as in prokaryotic mechanosensors or are they mediated through macromolecular tethers attached to the channel? Here we show in cells that the K(+) channel TRAAK (K2P4.1) is responsive to mechanical forces similar to the ion channel Piezo1 and that mechanical activation of TRAAK can electrically counter Piezo1 activation. We then show that the biophysical origins of force transduction in TRAAK and TREK1 (K2P2.1) two-pore domain K(+) (K2P) channels come from the lipid membrane, not from attached tethers. These findings extend the "force-from-lipid" principle established for prokaryotic mechanosensitive channels MscL and MscS to these eukaryotic mechanosensitive K(+) channels.
authors.affiliation: Laboratory of Molecular Neurobiology and Biophysics and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Brohawn
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Su
authors.forename: Roderick
authors.initials: R
authors.lastname: MacKinnon
mesh_terms: D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000502:physiology*; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D010843:Pichia; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*
chemical_list: D007473:Ion Channels; C503432:KCNK4 protein, human; C515204:PIEZO1 protein, human; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1
keywords: gating; mechanosensation; potassium channel; reconstitution; tension