TY  - JOUR
A1  - Bittner, Stefan
A1  - Bobak, Nicole
A1  - Hofmann, Majella-Sophie
A1  - Schuhmann, Michael K.
A1  - Ruck, Tobias
A1  - Göbel, Kerstin
A1  - Brück, Wolfgang
A1  - Wiendl, Heinz
A1  - Meuth, Sven G.
T1  - Murine K\(_{2P}\)5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K\(_{2P}\)3.1-and K\(_{V}\)1.3-Dependent Mechanisms
T2  - International Journal of Molecular Sciences
N2  - Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K\(_{2P}\)5.1(TASK2; KCNK5) channels belonging to the family of two-pore domain potassium channels have previously been correlated to the activity of autoreactive T lymphocytes in patients with multiple sclerosis and rheumatoid arthritis. In humans, K\(_{2P}\)5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation of targeting K\(_{2P}\)5.1 is currently hampered by a lack of highly selective inhibitors, making it necessary to evaluate the impact of KCNK5 in established preclinical animal disease models. We here demonstrate that K\(_{2P}\)5.1 knockout (K\(_{2P}\)5.1\(^{-/-}\) mice display no significant alterations concerning T cell cytokine production, proliferation rates, surface marker molecules or signaling pathways. In an experimental model of autoimmune neuroinflammation, K\(_{2P}\)5.1\(^{-/-}\) mice show a comparable disease course to wild-type animals and no major changes in the peripheral immune system or CNS compartment. A compensatory upregulation of the potassium channels K\(_{2P}\)3.1 and K\(_{V}\)1.3 seems to counterbalance the deletion of K\(_{2P}\)5.1. As an alternative model mimicking autoimmune neuroinflammation, experimental autoimmune encephalomyelitis in the common marmoset has been proposed, especially for testing the efficacy of new potential drugs. Initial experiments show that K\(_{2P}\)5.1 is functionally expressed on marmoset T lymphocytes, opening up the possibility for assessing future K\(_{2P}\)5.1-targeting drugs.
KW  - domain potassium channels
KW  - volume regulation
KW  - multiple-sclerosis
KW  - potassium channels
KW  - multiple sclerosis
KW  - ion channels
KW  - K+ channel
KW  - T lymphocytes
KW  - up-regulation
KW  - TASK2
KW  - K2P channels
KW  - B cells
KW  - ph
KW  - K\(_{2P}\)5.1
KW  - KCNK5
KW  - autoimmune neuroinflammation
KW  - EAE
Y1  - 2015
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/15145
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-151454
VL  - 16
SP  - 16880
EP  - 16896
ER  -