Blocking KV1.3 channels inhibits Th2 lymphocyte function and treats a rat model of asthma

J Biol Chem. 2014 May 2;289(18):12623-32. doi: 10.1074/jbc.M113.517037. Epub 2014 Mar 18.


Allergic asthma is a chronic inflammatory disease of the airways. Of the different lower airway-infiltrating immune cells that participate in asthma, T lymphocytes that produce Th2 cytokines play important roles in pathogenesis. These T cells are mainly fully differentiated CCR7(-) effector memory T (TEM) cells. Targeting TEM cells without affecting CCR7(+) naïve and central memory (TCM) cells has the potential of treating TEM-mediated diseases, such as asthma, without inducing generalized immunosuppression. The voltage-gated KV1.3 potassium channel is a target for preferential inhibition of TEM cells. Here, we investigated the effects of ShK-186, a selective KV1.3 channel blocker, for the treatment of asthma. A significant proportion of T lymphocytes in the lower airways of subjects with asthma expressed high levels of KV1.3 channels. ShK-186 inhibited the allergen-induced activation of peripheral blood T cells from those subjects. Immunization of F344 rats against ovalbumin followed by intranasal challenges with ovalbumin induced airway hyper-reactivity, which was reduced by the administration of ShK-186. ShK-186 also reduced total immune infiltrates in the bronchoalveolar lavage and number of infiltrating lymphocytes, eosinophils, and neutrophils assessed by differential counts. Rats with the ovalbumin-induced model of asthma had elevated levels of the Th2 cytokines IL-4, IL-5, and IL-13 measured by ELISA in their bronchoalveolar lavage fluids. ShK-186 administration reduced levels of IL-4 and IL-5 and induced an increase in the production of IL-10. Finally, ShK-186 inhibited the proliferation of lung-infiltrating ovalbumin-specific T cells. Our results suggest that KV1.3 channels represent effective targets for the treatment of allergic asthma.

Keywords: Airway Inflammation; Allergy; Animal Models; Asthma; Cellular Immune Response; KCNA3; KV1.3; Potassium Channels; T Lymphocyte; Therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Asthma / immunology*
  • Asthma / metabolism
  • Asthma / prevention & control
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / immunology
  • Disease Models, Animal*
  • Female
  • Flow Cytometry
  • Humans
  • Immunologic Memory / drug effects
  • Immunologic Memory / immunology
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism
  • Interleukin-13 / immunology
  • Interleukin-13 / metabolism
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism
  • Interleukin-5 / immunology
  • Interleukin-5 / metabolism
  • Kv1.3 Potassium Channel / antagonists & inhibitors
  • Kv1.3 Potassium Channel / immunology*
  • Kv1.3 Potassium Channel / metabolism
  • Male
  • Middle Aged
  • Ovalbumin / immunology
  • Potassium Channel Blockers / immunology
  • Potassium Channel Blockers / pharmacology
  • Proteins / immunology
  • Proteins / pharmacology
  • Rats
  • Rats, Inbred F344
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Young Adult


  • Interleukin-13
  • Interleukin-5
  • Kv1.3 Potassium Channel
  • Potassium Channel Blockers
  • Proteins
  • Shk-186 peptide
  • Interleukin-10
  • Interleukin-4
  • Ovalbumin