Volume regulation of murine T lymphocytes relies on voltage-dependent and two-pore domain potassium channels

Biochim Biophys Acta. 2011 Aug;1808(8):2036-44. doi: 10.1016/j.bbamem.2011.04.013. Epub 2011 May 5.

Abstract

A variety of ion channels are supposed to orchestrate the homoeostatic volume regulation in T lymphocytes. However, the relative contribution of different potassium channels to the osmotic volume regulation and in particular to the regulatory volume decrease (RVD) in T cells is far from clear. This study explores a putative role of the newly identified K(2P) channels (TASK1, TASK2, TASK3 and TRESK) along with the voltage-gated potassium channel K(V)1.3 and the calcium-activated potassium channel K(Ca)3.1 in the RVD of murine T lymphocytes, using genetic and pharmacological approaches. K(2P) channel knockouts exerted profound effects on the osmotic properties of murine T lymphocytes, as revealed by reduced water and RVD-related solute permeabilities. Moreover, both genetic and pharmacological data proved a key role of K(V)1.3 and TASK2 channels in the RVD of murine T cells exposed to hypotonic saline. Our experiments demonstrate a leading role of potassium channels in the osmoregulation of T lymphocytes under different conditions. In summary, the present study sheds new light on the complex and partially redundant network of potassium channels involved in the basic physiological process of the cellular volume homeostasis and extends the repertoire of potassium channels by the family of K(2P) channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Size* / drug effects
  • Cells, Cultured
  • Hypotonic Solutions
  • Kv1.3 Potassium Channel / antagonists & inhibitors
  • Kv1.3 Potassium Channel / metabolism*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Nerve Tissue Proteins / metabolism
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / metabolism
  • Potassium Channels, Tandem Pore Domain / antagonists & inhibitors
  • Potassium Channels, Tandem Pore Domain / deficiency
  • Potassium Channels, Tandem Pore Domain / genetics
  • Potassium Channels, Tandem Pore Domain / metabolism*
  • Saline Solution, Hypertonic
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism*
  • Time Factors
  • Water-Electrolyte Balance* / drug effects

Substances

  • Hypotonic Solutions
  • Kcna3 protein, mouse
  • Kcnk5 protein, mouse
  • Kv1.3 Potassium Channel
  • Nerve Tissue Proteins
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Tandem Pore Domain
  • Saline Solution, Hypertonic
  • TASK3 protein, mouse
  • Trik protein, mouse
  • potassium channel subfamily K member 3