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TWIK1, a unique background channel with variable ion selectivity

机译：TWIK1，具有可变离子选择性的独特背景通道

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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. TWIKT~(-/-) pancreatic β cells are more polarized than control cells, confirming a depolarizing role of TWIK1 in kidney and pancreatic cells.
机译：TWIK1属于具有两个孔结构域的背景K〜+通道家族。在天然和转染的细胞中，主要在回收内体中检测到TWIK1。在肾脏的主要细胞中，TWIK1基因失活会导致非选择性阳离子电导的丧失，这是归因于其他通道的适应性调节的意想不到的效果。在这里，我们显示TWIK1离子选择性受细胞外pH值的调节。尽管TWIK1在中性pH下具有K〜+选择性，但在内体中发现的酸性pH下它对Na〜+具有渗透性。恢复中性pH后，选择性恢复缓慢。这种滞后作用使TWIK1作为背景通道的作用似乎是合理的，在该背景通道中，选择性以及由此产生的抑制或兴奋性对细胞兴奋性的影响取决于其在内部酸性存储和质膜之间的再循环率。 TWIKT〜（-/-）胰腺β细胞的极化作用比对照细胞要强，这证实了TWIK1在肾脏和胰腺细胞中的去极化作用。

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    Franck C. Chatelain; Delphine Bichet; Dominique Douguet; Sylvain Feliciangeli; Said Bendahhou; Markus Reichold; Richard Warth; Jacques Barhanin; Florian Lesage;

  • 作者单位

    Laboratories of Excellence, Ion Channel Science and Therapeutics, 06560 Valbonne, France,Institut de Pharmacologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique, and 06560 Valbonne, France,Universite de Nice Sophia Antipolis, 06560 Valbonne, France;

    Laboratories of Excellence, Ion Channel Science and Therapeutics, 06560 Valbonne, France,Institut de Pharmacologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique, and 06560 Valbonne, France,Universite de Nice Sophia Antipolis, 06560 Valbonne, France;

    Laboratories of Excellence, Ion Channel Science and Therapeutics, 06560 Valbonne, France,Institut de Pharmacologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique, and 06560 Valbonne, France,Universite de Nice Sophia Antipolis, 06560 Valbonne, France;

    Laboratories of Excellence, Ion Channel Science and Therapeutics, 06560 Valbonne, France,Institut de Pharmacologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique, and 06560 Valbonne, France,Universite de Nice Sophia Antipolis, 06560 Valbonne, France;

    Laboratories of Excellence, Ion Channel Science and Therapeutics, 06560 Valbonne, France,Laboratoire de PhysioMedecine Moleculaire, Centre National de la Recherche Scientifique and 06108 Nice Cedex, France,Universite de Nice Sophia Antipolis, 06108 Nice Cedex, France;

    Department of Physiology, University of Regensburg, 93053 Regensburg, Germany;

    Department of Physiology, University of Regensburg, 93053 Regensburg, Germany;

    Laboratories of Excellence, Ion Channel Science and Therapeutics, 06560 Valbonne, France,Laboratoire de PhysioMedecine Moleculaire, Centre National de la Recherche Scientifique and 06108 Nice Cedex, France,Universite de Nice Sophia Antipolis, 06108 Nice Cedex, France;

    Laboratories of Excellence, Ion Channel Science and Therapeutics, 06560 Valbonne, France,Institut de Pharmacologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique, and 06560 Valbonne, France,Universite de Nice Sophia Antipolis, 06560 Valbonne, France;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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