The Volume Activated Potassium Channel KCNK5 is Up-Regulated in Activated Human T Cells, but Volume Regulation is Impaired

Cell Physiol Biochem. 2016;38(3):883-92. doi: 10.1159/000443042. Epub 2016 Feb 25.

Abstract

Background/aims: The potential role of the two-pore domain potassium channel KCNK5 (also known as TASK-2 and K(2P)5.1) in activated T cell physiology has only recently been described. So far KCNK5 has been described to be up-regulated in T cells in multiple sclerosis patients and to be implicated in the volume regulatory mechanism regulatory volume decrease (RVD) in T cells.

Methods: We investigated the time-dependent expression pattern of KCNK5 in CD3/CD28 activated human T cells using qPCR and Western blotting and its role in RVD using a Coulter Counter.

Results: KCNK5 is highly up-regulated in CD3/CD28 activated T cells both at mRNA (after 24 h) and protein level (72 and 144 h), but despite this up-regulation the RVD response is inhibited. Furthermore, the swelling-activated Cl- permeability in activated T cells is strongly decreased, and the RVD inhibition is predominantly due to the decreased Cl- permeability.

Conclusion: The up-regulated KCNK5 in activated human T cells does not play a volume regulatory role, due to decreased Cl- permeability. We speculate that the KCNK5 up-regulation might play a role in hyperpolarization of the cell membrane leading to increased Ca2+ influx and proliferation of T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD28 Antigens / metabolism
  • CD3 Complex / pharmacology
  • Calcium / metabolism
  • Cell Size / drug effects
  • Chlorine / metabolism
  • Humans
  • Intermediate-Conductance Calcium-Activated Potassium Channels / genetics
  • Lymphocyte Activation*
  • Potassium Channels, Tandem Pore Domain / genetics*
  • Potassium Channels, Tandem Pore Domain / metabolism*
  • T-Lymphocytes / metabolism*
  • Up-Regulation*

Substances

  • CD28 Antigens
  • CD3 Complex
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • KCNK5 protein, human
  • KCNN4 protein, human
  • Potassium Channels, Tandem Pore Domain
  • Chlorine
  • Calcium