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http://purl.uniprot.org/citations/20582984http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20582984http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Activation of T cells critically depends on potassium channels. We here characterize the impact of K(2P)5.1 (KCNK5; TASK2), a member of the 2-pore domain family of potassium channels, on T-cell function and demonstrate its putative relevance in a T-cell-mediated autoimmune disorder, multiple sclerosis (MS).

Methods

Expression of K(2P)5.1 was investigated on RNA and protein level in different immune cells and in MS patients' biospecimens (peripheral blood mononuclear cells, cerebrospinal fluid cells, brain tissue specimen). Functional consequences of K(2P)5.1 expression were analyzed using pharmacological modulation, small interfering RNA (siRNA), overexpression, electrophysiological recordings, and computer modeling.

Results

Human T cells constitutively express K(2P)5.1. After T-cell activation, a significant and time-dependent upregulation of K(2P)5.1 channel expression was observed. Pharmacological blockade of K(2P)5.1 or knockdown with siRNA resulted in reduced T-cell functions, whereas overexpression of K(2P)5.1 had the opposite effect. Electrophysiological recordings of T cells clearly dissected K(2P)5.1-mediated effects from other potassium channels. The pathophysiological relevance of these findings was demonstrated by a significant K(2P)5.1 upregulation in CD4(+) and CD8(+) T cells in relapsing/remitting MS (RRMS) patients during acute relapses as well as higher levels on CD8(+) T cells of clinically isolated syndrome, RRMS, and secondary progressive multiple sclerosis patients during clinically stable disease. T cells in the cerebrospinal fluid from MS patients exhibit significantly elevated K(2P)5.1 levels. Furthermore, K(2P)5.1-positive T cells can be found in inflammatory lesions in MS tissue specimens.

Interpretation

Selective targeting of K(2P)5.1 may hold therapeutic promise for MS and putatively other T-cell-mediated disorders."xsd:string
http://purl.uniprot.org/citations/20582984http://purl.org/dc/terms/identifier"doi:10.1002/ana.22010"xsd:string
http://purl.uniprot.org/citations/20582984http://purl.uniprot.org/core/author"Wiendl H."xsd:string
http://purl.uniprot.org/citations/20582984http://purl.uniprot.org/core/author"Meuth S.G."xsd:string
http://purl.uniprot.org/citations/20582984http://purl.uniprot.org/core/author"Bittner S."xsd:string
http://purl.uniprot.org/citations/20582984http://purl.uniprot.org/core/author"Bobak N."xsd:string
http://purl.uniprot.org/citations/20582984http://purl.uniprot.org/core/author"Budde T."xsd:string
http://purl.uniprot.org/citations/20582984http://purl.uniprot.org/core/author"Meuth P."xsd:string
http://purl.uniprot.org/citations/20582984http://purl.uniprot.org/core/author"Herrmann A.M."xsd:string
http://purl.uniprot.org/citations/20582984http://purl.uniprot.org/core/author"Stenner M.P."xsd:string
http://purl.uniprot.org/citations/20582984http://purl.uniprot.org/core/author"Gobel K."xsd:string
http://purl.uniprot.org/citations/20582984http://purl.uniprot.org/core/author"Hohn K.G."xsd:string
http://purl.uniprot.org/citations/20582984http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20582984http://purl.uniprot.org/core/name"Ann Neurol"xsd:string
http://purl.uniprot.org/citations/20582984http://purl.uniprot.org/core/pages"58-69"xsd:string
http://purl.uniprot.org/citations/20582984http://purl.uniprot.org/core/title"Upregulation of K2P5.1 potassium channels in multiple sclerosis."xsd:string
http://purl.uniprot.org/citations/20582984http://purl.uniprot.org/core/volume"68"xsd:string
http://purl.uniprot.org/citations/20582984http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20582984
http://purl.uniprot.org/citations/20582984http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20582984
http://purl.uniprot.org/uniprot/#_A0A0B6VPR3-mappedCitation-20582984http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20582984
http://purl.uniprot.org/uniprot/#_O95279-mappedCitation-20582984http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20582984
http://purl.uniprot.org/uniprot/A0A0B6VPR3http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/20582984
http://purl.uniprot.org/uniprot/O95279http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/20582984