Immunosuppressive effects of a Kv1.3 inhibitor

Cell Immunol. 2003 Feb;221(2):100-6. doi: 10.1016/s0008-8749(03)00063-7.

Abstract

The voltage gated potassium channel (Kv1.3) has been shown to play a role in immune responsiveness. Blockade of the channel led to diminution of T cell activation and delayed type hypersensitivity. Previous in vitro studies of the blockade were focused on T cell activation and proliferation. In this study we examined other T and monocytic cell mediated events to glean the extent of the immunosuppressive effects of a Kv1.3 specific inhibitor, Margatoxin (MgTX). We found that MgTX inhibited the intracellular production of Th-1 as well as Th-2 cytokines. MgTX can also inhibit IL-2 production and proliferation of T cells upon stimulation with anti-CD3 and VCAM-1. Furthermore, a redirected cytolytic activity was also inhibited by MgTX. However, MgTX did not inhibit generation of CTL to EBV transformed lymphoma cells or antibody-dependent cellular cytolysis mediated by monocytes. It appears that a Kv1.3 blockade does not affect all immune responses, particularly those of innate immunity.

MeSH terms

  • Antibody-Dependent Cell Cytotoxicity / drug effects
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Cell Division / drug effects
  • Cell Division / immunology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Flow Cytometry
  • Humans
  • Immunosuppressive Agents / immunology
  • Immunosuppressive Agents / pharmacology*
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / immunology
  • Ionomycin / immunology
  • Ionomycin / pharmacology
  • Ionophores / immunology
  • Ionophores / pharmacology
  • Kv1.3 Potassium Channel
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / immunology
  • Neurotoxins / immunology
  • Neurotoxins / pharmacology*
  • Potassium Channel Blockers / immunology
  • Potassium Channel Blockers / pharmacology*
  • Potassium Channels / immunology*
  • Potassium Channels / metabolism
  • Potassium Channels, Voltage-Gated*
  • Scorpion Venoms
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology
  • Tetradecanoylphorbol Acetate / immunology
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Cytokines
  • Immunosuppressive Agents
  • Ionophores
  • KCNA3 protein, human
  • Kv1.3 Potassium Channel
  • Neurotoxins
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Scorpion Venoms
  • Ionomycin
  • margatoxin
  • Tetradecanoylphorbol Acetate