TWIK-related acid-sensitive K+ channel 1 (TASK1) and TASK3 critically influence T lymphocyte effector functions

J Biol Chem. 2008 May 23;283(21):14559-70. doi: 10.1074/jbc.M800637200. Epub 2008 Mar 28.


Two major K(+) channels are expressed in T cells, (i) the voltage-dependent K(V)1.3 channel and (ii) the Ca(2+)-activated K(+) channel KCa 3.1 (IKCa channel). Both critically influence T cell effector functions in vitro and animal models in vivo. Here we identify and characterize TWIK-related acid-sensitive potassium channel 1 (TASK1) and TASK3 as an important third K(+) conductance on T lymphocytes. T lymphocytes constitutively express TASK1 and -3 protein. Application of semi-selective TASK blockers resulted in a significant reduction of cytokine production and cell proliferation. Interference with TASK channels on CD3(+) T cells revealed a dose-dependent reduction ( approximately 40%) of an outward current in patch clamp recordings indicative of TASK channels, a finding confirmed by computational modeling. In vivo relevance of our findings was addressed in an experimental model of multiple sclerosis, adoptive transfer experimental autoimmune encephalomyelitis. Pretreatment of myelin basic protein-specific encephalitogenic T lymphocytes with TASK modulators was associated with significant amelioration of the disease course in Lewis rats. These data introduce K(2)P channels as novel potassium conductance on T lymphocytes critically influencing T cell effector function and identify a possible molecular target for immunomodulation in T cell-mediated autoimmune disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Computational Biology
  • Disease Models, Animal
  • Electrophysiology
  • Encephalomyelitis / metabolism
  • Female
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Multiple Sclerosis / metabolism
  • Nerve Tissue Proteins / metabolism*
  • Patch-Clamp Techniques
  • Potassium / metabolism
  • Potassium Channels, Tandem Pore Domain / metabolism*
  • Rats
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*


  • Interleukin-2
  • KCNK9 protein, human
  • Nerve Tissue Proteins
  • Potassium Channels, Tandem Pore Domain
  • potassium channel subfamily K member 3
  • Interferon-gamma
  • Potassium