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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Douguet, Dominique Lesage, Florian Chatelain, Franck C. Bichet, Delphine Warth, Richard Barhanin, Jacques Feliciangeli, Sylvain Bendahhou, Saïd Reichold, Markus |
| Description | Author Affiliation: Chatelain FC ( Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, and Université de Nice Sophia Antipolis, 06560 Valbonne, France.); |
| 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 14 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Potassium Channels Metabolism Amino Acid Sequence Animals Hydrogen-Ion Concentration Models, Molecular Molecular Sequence Data Chemistry Sequence Homology, Amino Acid Xenopus Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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