title: Perspectives on the Two-Pore Domain Potassium Channel TREK-1 (TWIK-Related K(+) Channel 1). A Novel Therapeutic Target?
abstract: Potassium (K(+)) channels are membrane proteins expressed in most living cells that selectively control the flow of K(+) ions. More than 80 genes encode the K(+) channel subunits in the human genome. The TWIK-related K(+) channel (TREK-1) belongs to the two-pore domain K(+) channels (K2P) and displays various properties including sensitivity to physical (membrane stretch, acidosis, temperature) and chemical stimuli (signaling lipids, volatile anesthetics). The distribution of TREK-1 in the central nervous system, coupled with the physiological consequences of its opening and closing, leads to the emergence of this channel as an attractive therapeutic target. We review the TREK-1 channel, its structural and functional properties, and the pharmacological agents (agonists and antagonists) able to modulate its gating.
authors.affiliation: Université Clermont Auvergne, ENSCCF, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand, France.|CNRS, UMR6296, ICCF, F-63171 Aubiere, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Vivier
authors.affiliation: Université Clermont Auvergne, ENSCCF, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand, France.|CNRS, UMR6296, ICCF, F-63171 Aubiere, France.
authors.forename: Khalil
authors.initials: K
authors.lastname: Bennis
authors.affiliation: Labex ICST, Institut de Pharmacologie Moléculaire et Cellulaire, UMR CNRS 7275, Université de Nice Sophia Antipolis, F-06560 Valbonne, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Lesage
authors.affiliation: Université Clermont Auvergne, ENSCCF, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand, France.|CNRS, UMR6296, ICCF, F-63171 Aubiere, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ducki
mesh_terms: D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D003863:Depression / Q000188:drug therapy; D004827:Epilepsy / Q000188:drug therapy; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008958:Models, Molecular; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy; D024683:Potassium Channels, Tandem Pore Domain / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D018696:Neuroprotective Agents; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1