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

• Published in: Annals of neurology Vol. 60; no. 1; pp. 118 - 127
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2006; Willey-Liss
• Subjects: Adenoviridae - genetics; Adult; Aged; Biological and medical sciences; Brain - cytology; Brain - immunology; Central Nervous System Diseases - immunology; Central Nervous System Diseases - pathology; Dendritic Cells - drug effects; Dendritic Cells - physiology; Development. Senescence. Regeneration. Transplantation; Female; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; Genes, Dominant; Human viral diseases; Humans; Immunohistochemistry; Infectious diseases; Kv1.3 Potassium Channel - antagonists & inhibitors; Kv1.3 Potassium Channel - genetics; Kv1.3 Potassium Channel - metabolism; Kv1.5 Potassium Channel - antagonists & inhibitors; Kv1.5 Potassium Channel - genetics; Kv1.5 Potassium Channel - metabolism; Lipopolysaccharides - pharmacology; Male; Medical sciences; Middle Aged; Mutagenesis; Neurology; Patch-Clamp Techniques; Potassium Channel Blockers - pharmacology; Transfection; Vertebrates: nervous system and sense organs; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Dendritic cell; Nervous system diseases; Potassium; Central nervous system
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.20884

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 Kv1.3 and Kv1.5 in stimulated DCs with pharmacological blockers or with an inducible dominant‐negative Kv1.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 Kv1.3‐ and Kv1.5‐like channels at later stages of maturation. Kv1.3 and Kv1.5 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 Kv1.3 and Kv1.5 blockade. Interpretation These data support a functional role of Kv1.5 and Kv1.3 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