Altered neuronal expression of TASK1 and TASK3 potassium channels in rodent and human autoimmune CNS inflammation.
Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are characterized by T cell-mediated autoimmune inflammation of the central nervous system (CNS) leading to oligodendrocyte loss and demyelination accompanied by neuronal cell death. Neuronal TWIK-related acid-sensitive potassium (TASK) channels allow the regulated efflux of potassium ions. These channels might either protect neurons in the inflamed CNS by modulating electrical excitability or even contribute to inflammatory neurodegeneration mediating intracellular potassium depletion. Using a combination of in-situ-hybridisation and immunofluorescence staining, we found increased neuronal expression of TASK1 and TASK3 channels in the optic nerve and decreased expression in the spinal cord and thalamus of rats undergoing MOG-induced EAE. Inflammatory plaques of human MS patients displayed profoundly lowered expression of both TASK isoforms. Thus, regulated expression of TASK channels might contribute to a molecular switch between death and survival of neurons in autoimmune CNS inflammation.
Meuth
Sven G
SG
Department of Neurology, University of Würzburg, Josef-Schneider-Strafe 11, 97080 Würzburg, Germany. meuth_s@klinik.uni-wuerzburg.de
Kanyshkov
Tatjana
T
Melzer
Nico
N
Bittner
Stefan
S
Kieseier
Bernd C
BC
Budde
Thomas
T
Wiendl
Heinz
H
D000818:Animals; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D017403:In Situ Hybridization; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000276:immunology / Q000378:metabolism*; D009900:Optic Nerve / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011188:Potassium / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013788:Thalamus / Q000276:immunology / Q000378:metabolism / Q000473:pathology
C498655:KCNK9 protein, human; C407082:Kcnk9 protein, rat; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D011188:Potassium