Kv3.4 channel function and dysfunction in nociceptors

Channels (Austin). 2015;9(4):209-17. doi: 10.1080/19336950.2015.1056949. Epub 2015 Jun 3.

Abstract

Recently, we reported the isolation of the Kv3.4 current in dorsal root ganglion (DRG) neurons and described dysregulation of this current in a spinal cord injury (SCI) model of chronic pain. These studies strongly suggest that rat Kv3.4 channels are major regulators of excitability in DRG neurons from pups and adult females, where they help determine action potential (AP) repolarization and spiking properties. Here, we characterized the Kv3.4 current in rat DRG neurons from adult males and show that it transfers 40-70% of the total repolarizing charge during the AP across all ages and sexes. Following SCI, we also found remodeling of the repolarizing currents during the AP. In the light of these studies, homomeric Kv3.4 channels expressed in DRG nociceptors are emerging novel targets that may help develop new approaches to treat neuropathic pain.

Keywords: Kv3.4; action potential; pain; potassium channel; spinal cord injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / genetics
  • Action Potentials / physiology
  • Animals
  • Cells, Cultured
  • Female
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / physiology*
  • Gene Expression
  • Male
  • Neurons / metabolism
  • Neurons / physiology*
  • Nociceptors / metabolism
  • Nociceptors / physiology*
  • Patch-Clamp Techniques
  • RNA Interference
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Shaw Potassium Channels / genetics
  • Shaw Potassium Channels / physiology*

Substances

  • Kcnc4 protein, rat
  • Shaw Potassium Channels