Extracellular K+ and opening of voltage-gated potassium channels activate T cell integrin function: Physical and functional association between Kv1.3 channels and β1 integrins

Mia Levite, Liora Cahalon, Asher Peretz, Rami Hershkoviz, Alex Sobko, Amiram Ariel, Rooma Desai, Bernard Attali, Ofer Lider

Research output: Contribution to journalArticlepeer-review

Abstract

Elevated extracellular K+ ([K+](o)), in the absence of 'classical' immunological stimulatory signals, was found to itself be a sufficient stimulus to activate T cell β1 integrin moieties, and to induce integrin- mediated adhesion and migration. Gating of T cell voltage-gated K+ channels (Kv1.3) appears to be the crucial 'decision-making' step, through which various physiological factors, including elevated [K+](o) levels, affect the T cell β1 integrin function: opening of the channel leads to function, whereas its blockage prevents it. In support of this notion, we found that the proadhesive effects of the chemokine macrophage-inflammatory protein 1β, the neuropeptide calcitonin gene-related peptide (CGRP), as well as elevated [K+](o) levels, are blocked by specific Kv1.3 channel blockers, and that the unique physiological ability of substance P to inhibit T cell adhesion correlates with Kv1.3 inhibition. Interestingly, the Kv1.3 channels and the β1 integrins coimmunoprecipitate, suggesting that their physical association underlies their functional cooperation on the T cell surface. This study shows that T cells can be activated and driven to integrin function by a pathway that does not involve any of its specific receptors (i.e., by elevated [K+](o)). In addition, our results suggest that undesired T cell integrin function in a series of pathological conditions can be arrested by molecules that block the Kv1.3 channels.

Original languageEnglish
Pages (from-to)1167-1176
Number of pages10
JournalJournal of Experimental Medicine
Volume191
Issue number7
DOIs
StatePublished - 3 Apr 2000
Externally publishedYes

Keywords

  • Extracellular K
  • Integrins
  • Neuroimmunomodulation
  • Potassium channels
  • T cells

Fingerprint

Dive into the research topics of 'Extracellular K+ and opening of voltage-gated potassium channels activate T cell integrin function: Physical and functional association between Kv1.3 channels and β1 integrins'. Together they form a unique fingerprint.

Cite this