Long-term actions of interleukin-1β on K+, Na+ and Ca2+ channel currents in small, IB4-positive dorsal root ganglion neurons; possible relevance to the etiology of neuropathic pain

Myung-Chul Noh; Patrick L Stemkowski; Peter A Smith

doi:10.1016/j.jneuroim.2019.05.002

Long-term actions of interleukin-1β on K⁺, Na⁺ and Ca²⁺ channel currents in small, IB₄-positive dorsal root ganglion neurons; possible relevance to the etiology of neuropathic pain

J Neuroimmunol. 2019 Jul 15:332:198-211. doi: 10.1016/j.jneuroim.2019.05.002. Epub 2019 May 4.

Authors

Myung-Chul Noh¹, Patrick L Stemkowski², Peter A Smith³

Affiliations

¹ Department of Pharmacology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
² Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
³ Department of Pharmacology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta T6G 2H7, Canada. Electronic address: pas3@ualberta.ca.

PMID: 31077855
DOI: 10.1016/j.jneuroim.2019.05.002

Abstract

Excitation of dorsal root ganglion (DRG) neurons by interleukin 1β (IL-1β) is implicated in the onset of neuropathic pain. To understand its mechanism of action, isolectin B4 positive (IB₄⁺) DRG neurons were exposed to 100pM IL-1β for 5-6d. A reversible increase in action potential (AP) amplitude reflected increased TTX-sensitive sodium current (TTX-S I_Na). An irreversible increase in AP duration reflected decreased Ca²⁺- sensitive K⁺ conductance (BK(Ca) channels). Different processes thus underlie regulation of the two channel types. Since changes in AP shape facilitated Ca²⁺ influx, this explains how IL-1β facilitates synaptic transmission in the dorsal horn; thereby provoking pain.

Keywords: BK(Ca) channel; Electrophysiology; Ion channel; K(+) channel; Na(+) channel; Nerve injury; Neuroinflammation; Nociceptor; Peripheral neuropathy; Primary afferent.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Action Potentials / drug effects
Animals
Calcium Channels / drug effects*
Calcium Channels / metabolism
Cell Size
Ganglia, Spinal / cytology*
Glial Cell Line-Derived Neurotrophic Factor / pharmacology
Interleukin-1beta / pharmacology*
Ion Channel Gating / drug effects*
Male
Nerve Growth Factor / pharmacology
Neuralgia / etiology*
Neuralgia / metabolism
Patch-Clamp Techniques
Peptides / pharmacology
Plant Lectins / analysis
Potassium Channels / drug effects*
Potassium Channels / metabolism
Rats
Rats, Sprague-Dawley
Sensory Receptor Cells / drug effects*
Sensory Receptor Cells / metabolism
Sensory Receptor Cells / ultrastructure
Sodium Channels / drug effects*
Sodium Channels / metabolism

Substances

Calcium Channels
Glial Cell Line-Derived Neurotrophic Factor
Griffonia simplicifolia lectins
Interleukin-1beta
Peptides
Plant Lectins
Potassium Channels
Sodium Channels
tetrodotoxin-binding protein
iberiotoxin
Nerve Growth Factor

Grants and funding

HOP 126788/CIHR/Canada