title: TWIK1, a unique background channel with variable ion selectivity.
abstract: TWIK1 belongs to the family of background K(+) channels with two pore domains. In native and transfected cells, TWIK1 is detected mainly in recycling endosomes. In principal cells in the kidney, TWIK1 gene inactivation leads to the loss of a nonselective cationic conductance, an unexpected effect that was attributed to adaptive regulation of other channels. Here, we show that TWIK1 ion selectivity is modulated by extracellular pH. Although TWIK1 is K(+) selective at neutral pH, it becomes permeable to Na(+) at the acidic pH found in endosomes. Selectivity recovery is slow after restoration of a neutral pH. Such hysteresis makes plausible a role of TWIK1 as a background channel in which selectivity and resulting inhibitory or excitatory influences on cell excitability rely on its recycling rate between internal acidic stores and the plasma membrane. TWIK1(-/-) pancreatic β cells are more polarized than control cells, confirming a depolarizing role of TWIK1 in kidney and pancreatic cells.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, and Université de Nice Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Franck C
authors.initials: FC
authors.lastname: Chatelain
authors.forename: Delphine
authors.initials: D
authors.lastname: Bichet
authors.forename: Dominique
authors.initials: D
authors.lastname: Douguet
authors.forename: Sylvain
authors.initials: S
authors.lastname: Feliciangeli
authors.forename: Saïd
authors.initials: S
authors.lastname: Bendahhou
authors.forename: Markus
authors.initials: M
authors.lastname: Reichold
authors.forename: Richard
authors.initials: R
authors.lastname: Warth
authors.forename: Jacques
authors.initials: J
authors.lastname: Barhanin
authors.forename: Florian
authors.initials: F
authors.lastname: Lesage
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
chemical_list: D015221:Potassium Channels