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Potassium channels K v 1.3 and K v 1.5 are expressed on blood‐derived dendritic cells in the central nervous system
Author(s) -
Mullen Katherine M.,
Rozycka Monika,
Rus Horea,
Hu Lina,
Cudrici Cornelia,
Zafranskaia Ekaterina,
Pennington Michael W.,
Johns David C.,
Judge Susan I. V.,
Calabresi Peter A.
Publication year - 2006
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20884
Subject(s) - cd80 , multiple sclerosis , cd86 , potassium channel , 4 aminopyridine , neuroscience , downregulation and upregulation , potassium channel blocker , immune system , central nervous system , patch clamp , cd40 , electrophysiology , chemistry , medicine , immunology , biology , t cell , cytotoxic t cell , biochemistry , gene , in vitro
Objective Potassium (K + ) channels on immune cells have gained attention recently as promising targets of therapy for immune‐mediated neurological diseases such as multiple sclerosis (MS). We examined K + channels on dendritic cells (DCs), which infiltrate the brain in MS and may impact disease course. Methods We identified K + channels on blood‐derived DCs by whole‐cell patch‐clamp analysis, confirmed by immunofluorescent staining. We also stained K + channels in brain sections from MS patients and control subjects. To test functionality, we blocked K v 1.3 and K v 1.5 in stimulated DCs with pharmacological blockers or with an inducible dominant‐negative K v 1.x adenovirus construct and analyzed changes in costimulatory molecule upregulation. Results Electrophysiological analysis of DCs showed an inward‐rectifying K + current early after stimulation, replaced by a mix of voltage‐gated K v 1.3‐ and K v 1.5‐like channels at later stages of maturation. K v 1.3 and K v 1.5 were also highly expressed on DCs infiltrating MS brain tissue. Of note, we found that CD83, CD80, CD86, CD40, and interleukin‐12 upregulation were significantly impaired on K v 1.3 and K v 1.5 blockade. Interpretation These data support a functional role of K v 1.5 and K v 1.3 on activated human DCs and further define the mechanisms by which K + channel blockade may act to suppress immune‐mediated neurological diseases. Ann Neurol 2006