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

Katherine M. Mullen, Monika Rozycka, Horea Rus, Lina Hu, Cornelia Cudrici, Ekaterina Zafranskaia, Michael W. Pennington, David C. Johns, Susan I.V. Judge, Peter A. Calabresi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)118-127
Number of pages10
JournalAnnals of neurology
Volume60
Issue number1
DOIs
StatePublished - Jul 2006

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Potassium channels K<sub>v</sub>1.3 and K<sub>v</sub>1.5 are expressed on blood-derived dendritic cells in the central nervous system'. Together they form a unique fingerprint.

Cite this