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Identification of two-pore domain potassium channels as potent modulators of osmotic volume regulation in human T lymphocytes

: Andronic, J.; Bobak, N.; Bittner, S.; Ehling, P.; Kleinschnitz, C.; Herrmann, A.M.; Zimmermann, H.; Sauer, M.; Wiendl, H.; Budde, T.; Meuth, S.G.; Sukhorukov, V.L.


Biochimica et Biophysica Acta. Biomembranes 1828 (2013), No.2, pp.699-707
ISSN: 0005-2736
ISSN: 1879-2642
Deutsche Forschungsgemeinschaft DFG
FOR 1086; ME 3283/1-2, TP2
Journal Article
Fraunhofer IBMT ()

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.