Kv1.3/Kv1.5 heteromeric channels compromise pharmacological responses in macrophages

Biochem Biophys Res Commun. 2007 Jan 26;352(4):913-8. doi: 10.1016/j.bbrc.2006.11.120. Epub 2006 Dec 4.

Abstract

Voltage-dependent K(+) (Kv) channels are involved in the immune response. Kv1.3 is highly expressed in activated macrophages and T-effector memory cells of autoimmune disease patients. Macrophages are actively involved in T-cell activation by cytokine production and antigen presentation. However, unlike T-cells, macrophages express Kv1.5, which is resistant to Kv1.3-drugs. We demonstrate that mononuclear phagocytes express different Kv1.3/Kv1.5 ratios, leading to biophysically and pharmacologically distinct channels. Therefore, Kv1.3-based treatments to alter physiological responses, such as proliferation and activation, are impaired by Kv1.5 expression. The presence of Kv1.5 in the macrophagic lineage should be taken into account when designing Kv1.3-based therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biophysical Phenomena
  • Biophysics
  • Cells, Cultured
  • Kv1.3 Potassium Channel / metabolism*
  • Kv1.5 Potassium Channel / metabolism*
  • Macrophages / drug effects*
  • Macrophages / metabolism*
  • Mice
  • Scorpion Venoms / pharmacology

Substances

  • Kv1.3 Potassium Channel
  • Kv1.5 Potassium Channel
  • Scorpion Venoms
  • margatoxin