Volume regulation of murine T lymphocytes relies on voltage-dependent and two-pore domain potassium channels

Volume regulation of murine T lymphocytes relies on voltage-dependent and two-pore domain potassium channels
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DOI:
10.1016/j.bbamem.2011.04.013
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发表时间:
2011-08-01
影响因子:
3.4
通讯作者:
Sukhorukov, Vladimir L.
Sukhorukov, Vladimir L.
中科院分区:
生物学3区
文献类型:
--
作者:
Bobak, Nicole;Bittner, Stefan;Sukhorukov, Vladimir L.

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多种离子通道被认为协调T淋巴细胞的恒定容量调节。然而,不同钾通道对T细胞渗透量调节,特别是调节性体积减小(RVD)的相对贡献还远不清楚。本研究采用遗传学和药理学方法,探讨了新发现的K-2P通道(TASK1、TASK2、TASK3和Tresk)以及电压门控性钾通道K(V)1.3和钙激活钾通道K(Ca)3.1在小鼠T淋巴细胞RVD中的可能作用。K-2P通道敲除对小鼠T淋巴细胞的渗透特性有深远的影响,表现为水和RVD相关的溶质通透性降低。此外,遗传学和药理学数据都证明了K(V)1.3和TASK2通道在低渗盐水暴露的小鼠T细胞RVD中起关键作用。我们的实验表明,钾通道在不同条件下对T淋巴细胞的渗透调节起主导作用。综上所述,本研究揭示了参与细胞体积内稳态基本生理过程的复杂和部分冗余的钾通道网络,并通过K-2P通道家族扩展了钾通道的谱系。(C)2011年爱思唯尔房车。版权所有。
A variety of ion channels are supposed to orchestrate the homoeostatic volume regulation in T lymphocytes. However, the relative contribution of different potassium channels to the osmotic volume regulation and in particular to the regulatory volume decrease (RVD) in T cells is far from clear. This study explores a putative role of the newly identified K-2P channels (TASK1, TASK2, TASK3 and TRESK) along with the voltage-gated potassium channel K(V)1.3 and the calcium-activated potassium channel K(Ca)3.1 in the RVD of murine T lymphocytes, using genetic and pharmacological approaches. K-2P channel knockouts exerted profound effects on the osmotic properties of murine T lymphocytes, as revealed by reduced water and RVD-related solute permeabilities. Moreover, both genetic and pharmacological data proved a key role of K(V)1.3 and TASK2 channels in the RVD of murine T cells exposed to hypotonic saline. Our experiments demonstrate a leading role of potassium channels in the osmoregulation of T lymphocytes under different conditions. In summary, the present study sheds new light on the complex and partially redundant network of potassium channels involved in the basic physiological process of the cellular volume homeostasis and extends the repertoire of potassium channels by the family of K-2P channels. (C) 2011 Elsevier RV. All rights reserved.