Identification of two-pore domain potassium channels as potent modulators of osmotic volume regulation in human T lymphocytes
Identification of two-pore domain potassium channels as potent modulators of osmotic volume regulation in human T lymphocytes
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DOI：
10.1016/j.bbamem.2012.09.028
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发表时间：
2013-02-01
影响因子：
3.4
通讯作者：
Sukhorukov, Vladimir L.
中科院分区：
文献类型：
--
作者：
Andronic, Joseph;Bobak, Nicole;Sukhorukov, Vladimir L.
T淋巴细胞的许多功能与细胞体积的动态平衡和调节密切相关，它利用一个复杂的膜通道网络来处理阴离子和阳离子。在各种钾通道中，电压门控的K(V)1.3对渗透调节，特别是低渗环境下T细胞调节性体积减少(RVD)时钾的释放起着重要的作用。在这里，我们讨论了新发现的两孔结构域(K-2P)通道在人类CD4(+)T淋巴细胞RVD中的假定作用，使用了一系列有效的众所周知的通道阻滞剂。在本研究中，抑制RVD的药理学特征显示K(2P)5.1和K(2P)18.1是参与原始和刺激T细胞RVD的最重要的K-2P通道。化学抑制K(2P)5.1和K(2P)18.1对RVD的影响与K(V)1.3相当。K(2P)9.1对T细胞的RVD也有显著的贡献，但这种贡献的程度及其对激活状态的依赖并不能明确地解决。综上所述，我们的数据首次提供了人类T淋巴细胞RVD相关钾外流依赖于K-2P通道的证据。(C)2012爱思唯尔B.V.保留所有权利。
Many functions of T lymphocytes are closely related to cell volume homeostasis and regulation, which utilize a complex network of membrane channels for anions and cations. Among the various potassium channels, the voltage-gated K(v)1.3 is well known to contribute greatly to the osmoregulation and particularly to the potassium release during the regulatory volume decrease (RVD) of T cells faced with hypotonic environment. Here we address a putative role of the newly identified two-pore domain (K-2P) channels in the RVD of human CD4(+) T lymphocytes, using a series of potent well known channel blockers. In the present study, the pharmacological profiles of RVD inhibition revealed K(2P)5.1 and K(2P)18.1 as the most important K-2P channels involved in the RVD of both naive and stimulated T cells. The impact of chemical inhibition of K(2P)5.1 and K(2P)18.1 on the RVD was comparable to that of K(v)1.3. K(2P)9.1 also notably contributed to the RVD of T cells but the extent of this contribution and its dependence on the activation status could not be unambiguously resolved. In summary, our data provide first evidence that the RVD-related potassium efflux from human T lymphocytes relies on K-2P channels. (C) 2012 Elsevier B.V. All rights reserved.