Bobak Nicole, Bittner Stefan, Andronic Joseph, Hartmann Susanne, Mühlpfordt Friederike, Schneider-Hohendorf Tilman, Wolf Karen, Schmelter Carsten, Göbel Kerstin, Meuth Patrick, Zimmermann Heiko, Döring Frank, Wischmeyer Erhard, Budde Thomas, Wiendl Heinz, Meuth Sven G, Sukhorukov Vladimir L
University of Muenster, Department of Neurology - Inflammatory Disorders of the Nervous System and Neurooncology, Domagkstr, 13, 48149 Muenster, Germany.
Biochim Biophys Acta. 2011 Aug;1808(8):2036-44. doi: 10.1016/j.bbamem.2011.04.013. Epub 2011 May 5.
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.
多种离子通道被认为在T淋巴细胞的稳态容积调节中发挥协同作用。然而，不同钾通道对T细胞渗透容积调节，尤其是对调节性容积减小（RVD）的相对贡献仍远未明确。本研究采用遗传学和药理学方法，探讨新发现的K(2P)通道（TASK1、TASK2、TASK3和TRESK）以及电压门控钾通道K(V)1.3和钙激活钾通道K(Ca)3.1在小鼠T淋巴细胞RVD中的假定作用。K(2P)通道基因敲除对小鼠T淋巴细胞的渗透特性产生了深远影响，这表现为水和与RVD相关的溶质通透性降低。此外，遗传学和药理学数据均证明，K(V)1.3和TASK2通道在暴露于低渗盐水的小鼠T细胞的RVD中起关键作用。我们的实验证明了钾通道在不同条件下T淋巴细胞渗透调节中的主导作用。总之，本研究为参与细胞容积稳态这一基本生理过程的复杂且部分冗余的钾通道网络提供了新的认识，并通过K(2P)通道家族扩展了钾通道的种类。
