Potassium channels Kv1.3 and Kv1.5 are expressed on blood-derived dendritic cells in the central nervous system.
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.


CONCLUSIONS
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.
Mullen
Katherine M
KM
Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Rozycka
Monika
M
Rus
Horea
H
Hu
Lina
L
Cudrici
Cornelia
C
Zafranskaia
Ekaterina
E
Pennington
Michael W
MW
Johns
David C
DC
Judge
Susan I V
SI
Calabresi
Peter A
PA
D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000368:Aged; D001921:Brain / Q000166:cytology / Q000276:immunology*; D002493:Central Nervous System Diseases / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005799:Genes, Dominant; D006801:Humans; D007150:Immunohistochemistry; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051666:Kv1.5 Potassium Channel / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D016296:Mutagenesis; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D014162:Transfection
C496981:KCNA5 protein, human; D051664:Kv1.3 Potassium Channel; D051666:Kv1.5 Potassium Channel; D008070:Lipopolysaccharides; D026902:Potassium Channel Blockers