title: Multiple modalities converge on a common gate to control K2P channel function.
abstract: Members of the K(2P) potassium channel family regulate neuronal excitability and are implicated in pain, anaesthetic responses, thermosensation, neuroprotection, and mood. Unlike other potassium channels, K(2P)s are gated by remarkably diverse stimuli that include chemical, thermal, and mechanical modalities. It has remained unclear whether the various gating inputs act through separate or common channel elements. Here, we show that protons, heat, and pressure affect activity of the prototypical, polymodal K(2P), K(2P)2.1 (KCNK2/TREK-1), at a common molecular gate that comprises elements of the pore-forming segments and the N-terminal end of the M4 transmembrane segment. We further demonstrate that the M4 gating element is conserved among K(2P)s and is employed regardless of whether the gating stimuli are inhibitory or activating. Our results define a unique gating mechanism shared by K(2P) family members and suggest that their diverse sensory properties are achieved by coupling different molecular sensors to a conserved core gating apparatus.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, 94158-9001, USA.
authors.forename: Sviatoslav N
authors.initials: SN
authors.lastname: Bagriantsev
authors.forename: Rémi
authors.initials: R
authors.lastname: Peyronnet
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Clark
authors.forename: Eric
authors.initials: E
authors.lastname: Honoré
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Minor
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006358:Hot Temperature; D015640:Ion Channel Gating; D051379:Mice; D008969:Molecular Sequence Data; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000502:physiology*; D011312:Pressure; D011522:Protons
chemical_list: D024683:Potassium Channels, Tandem Pore Domain; D011522:Protons; C103742:potassium channel protein TREK-1