Potassium channels K_v1.3 and K_v1.5 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_v1.3 and K_v1.5 in stimulated DCs with pharmacological blockers or with an inducible dominant-negative K_v1.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_v1.3 and K_v1.5-like channels at later stages of maturation. K_v1.3 and K_v1.5 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_v1.3 and K_v1.5 blockade. Interpretation: These data support a functional role of K_v1.5 and K_v1.3 on activated human DCs and further define the mechanisms by which K⁺ channel blockade may act to suppress immune-mediated neurological diseases.