Kirkegaard Signe S, Strøm Pernille Dyhl, Gammeltoft Steen, Hansen Anker Jon, Hoffmann Else K
Section for Cell and Developmental Biology, University of Copenhagen, Copenhagen, Denmark.
Cell Physiol Biochem. 2016;38(3):883-92. doi: 10.1159/000443042. Epub 2016 Feb 25.
BACKGROUND/AIMS: The potential role of the two-pore domain potassium channel KCNK5 (also known as TASK-2 and K(2P)5.1) in activated T cell physiology has only recently been described. So far KCNK5 has been described to be up-regulated in T cells in multiple sclerosis patients and to be implicated in the volume regulatory mechanism regulatory volume decrease (RVD) in T cells.
We investigated the time-dependent expression pattern of KCNK5 in CD3/CD28 activated human T cells using qPCR and Western blotting and its role in RVD using a Coulter Counter.
KCNK5 is highly up-regulated in CD3/CD28 activated T cells both at mRNA (after 24 h) and protein level (72 and 144 h), but despite this up-regulation the RVD response is inhibited. Furthermore, the swelling-activated Cl- permeability in activated T cells is strongly decreased, and the RVD inhibition is predominantly due to the decreased Cl- permeability.
The up-regulated KCNK5 in activated human T cells does not play a volume regulatory role, due to decreased Cl- permeability. We speculate that the KCNK5 up-regulation might play a role in hyperpolarization of the cell membrane leading to increased Ca2+ influx and proliferation of T cells.
背景/目的：双孔域钾通道KCNK5（也称为TASK-2和K(2P)5.1）在活化T细胞生理学中的潜在作用直到最近才被描述。到目前为止，KCNK5已被描述为在多发性硬化症患者的T细胞中上调，并与T细胞中的容积调节机制——调节性容积减小（RVD）有关。
我们使用qPCR和蛋白质印迹法研究了KCNK5在CD3/CD28活化的人T细胞中的时间依赖性表达模式，并使用库尔特计数器研究了其在RVD中的作用。
KCNK5在CD3/CD28活化的T细胞中，无论是在mRNA水平（24小时后）还是蛋白质水平（72和144小时）均高度上调，但尽管有这种上调，RVD反应仍受到抑制。此外，活化T细胞中肿胀激活的Cl-通透性显著降低，RVD抑制主要归因于Cl-通透性降低。
由于Cl-通透性降低，活化的人T细胞中上调的KCNK5不发挥容积调节作用。我们推测KCNK5上调可能在细胞膜超极化中起作用，导致Ca2+内流增加和T细胞增殖。
