title: Molecular basis of the voltage-dependent gating of TREK-1, a mechano-sensitive K(+) channel.
abstract: TREK-1 is a member of the mammalian two P domain K(+) channel family. Mouse TREK-1 activity, in transiently transfected COS cells, is reduced at negative resting membrane potentials by both an external Mg(2+) block and an intrinsic voltage-dependent gating mechanism leading to a strong outward rectification. Deletional and chimeric analysis demonstrates that the carboxy terminal domain of TREK-1, but not the PKA phosphorylation site S333, is responsible for voltage-dependent gating. Since the same region is also critically required for TREK-1 mechano-gating, both mechanisms might be functionally linked. Preferential opening of TREK-1 at depolarized potentials will greatly affect action potential duration, recovery from inactivation and neuronal repetitive firing activity.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, UMR 6097, Sophia Antipolis, Valbonne, France.
authors.forename: François
authors.initials: F
authors.lastname: Maingret
authors.forename: Eric
authors.initials: E
authors.lastname: Honoré
authors.forename: Michel
authors.initials: M
authors.lastname: Lazdunski
authors.forename: Amanda Jane
authors.initials: AJ
authors.lastname: Patel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001696:Biomechanical Phenomena; D019556:COS Cells; D004553:Electric Conductivity; D006801:Humans; D015640:Ion Channel Gating; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D011993:Recombinant Fusion Proteins; C103742:potassium channel protein TREK-1; D008274:Magnesium