The potassium channel KCNK3 determines calcium signaling pathways in T lymphocytes
-
1
University of Muenster, Germany
Ion channels are known to influence the activation and effector functions of T lymphocytes. Recently, a role for members of the two-pore domain potassium channel family (K2P channels, e.g. KCNK3, KCNK5, KCNK9) could be described for autoimmune neuroinflammation. KCNK3-/- mice showed a significantly ameliorated disease course in myelin oligodendrocyte glycoprotein peptide induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. However, the underlying intracellular pathways in T cells have not yet been addressed. Therefore, we intended to investigate the influence of KCNK3 to intracellular T cell signaling.
Murine and human CD4+ T lymphocytes were stained with the calcium-sensitive dye Fura-2. Pharmacological blockade of KCNK3 with A293, a novel selective blocker, reduced the extracellular calcium influx upon T cell receptor (TCR) crosslink. These results could be confirmed with KCNK3-/- cells which displayed a significantly reduced calcium increase compared to wildtype mice. A293 had no additional effect on KCNK3-/- cells. The reduced calcium levels led to a reduced activation of calcineurin and therefore a reduced dephosphorylation and nuclear translocation of the calcium-dependent signaling protein nuclear factor of activated T-cells (NFAT) as detected by western blotting experiments. In contrast, upstream signaling proteins such as ZAP70 or LAT showed higher phosphorylation levels in KCNK3-/- mice than in wildtype mice both under basal and stimulated conditions.
In summary, we were able to demonstrate a crucial influence of KCNK3 on calcium signaling pathways in T cells. Further studies are needed to explore the molecular pathways in more detail.
Keywords:
T lymphocytes,
Ion Channels,
Potassium Channels,
Calcium,
signaling
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune receptors and signaling
Citation:
Bittner
S,
Wiendl
H and
Meuth
SG
(2013). The potassium channel KCNK3 determines calcium signaling pathways in T lymphocytes.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00625
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
12 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Stefan Bittner, University of Muenster, Muenster, Germany, stefan.bittner@unimedizin-mainz.de