title: Alternative translation initiation in rat brain yields K2P2.1 potassium channels permeable to sodium.
abstract: K(2P) channels mediate potassium background currents essential to central nervous system function, controlling excitability by stabilizing membrane potential below firing threshold and expediting repolarization. Here, we show that alternative translation initiation (ATI) regulates function of K(2P)2.1 (TREK-1) via an unexpected strategy. Full-length K(2P)2.1 and an isoform lacking the first 56 residues of the intracellular N terminus (K(2P)2.1Delta1-56) are produced differentially in a regional and developmental manner in the rat central nervous system, the latter passing sodium under physiological conditions leading to membrane depolarization. Control of ion selectivity via ATI is proposed to be a natural, epigenetic mechanism for spatial and temporal regulation of neuronal excitability.
authors.affiliation: Department of Pediatrics and Institute for Molecular Pediatric Sciences, Pritzker School of Medicine, University of Chicago, 5721 South Maryland Avenue, Chicago, IL 60637, USA.
authors.forename: Dierk
authors.initials: D
authors.lastname: Thomas
authors.forename: Leigh D
authors.initials: LD
authors.lastname: Plant
authors.forename: Christina M
authors.initials: CM
authors.lastname: Wilkens
authors.forename: Zoe A
authors.initials: ZA
authors.lastname: McCrossan
authors.forename: Steve A N
authors.initials: SA
authors.lastname: Goldstein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000502:physiology*; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D010539:Permeability; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics* / Q000378:metabolism*; D014176:Protein Biosynthesis; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D012964:Sodium