4.8 Article

TWIK1, a unique background channel with variable ion selectivity

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NATL ACAD SCIENCES
DOI: 10.1073/pnas.1201132109

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  1. Fondation pour la Recherche Medicale (Equipe labellisee Fondation pour la Recherche Medicale)
  2. Contrat Hospitalier de Recherche Translationnelle, Service de Neurologie, Centre Hospitalier Universitaire de Nice
  3. Association pour la Recherche sur le Cancer
  4. Agence Nationale de la Recherche

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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 beta cells are more polarized than control cells, confirming a depolarizing role of TWIK1 in kidney and pancreatic cells.

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