期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2012
卷号：109
期号：14
页码：5499-5504
DOI：10.1073/pnas.1201132109
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
