Ileitis modulates potassium and sodium currents in guinea pig dorsal root ganglia sensory neurons.

Abstract

Intestinal inflammation induces hyperexcitability of dorsal root ganglia sensory neurons, which has been implicated in increased pain sensation. This study examined whether alteration of sodium (Na+) and/or potassium (K+) currents underlies this hyperexcitability. Ileitis was induced in guinea pig ileum with trinitrobenzene sulphonic acid (TBNS) and dorsal root ganglion neurons innervating the site of inflammation were identified by Fast Blue or DiI fluorescence labelling. Whole cell recordings were made from acutely dissociated small-sized neurons at 7-10 days. Neurons exhibited transient A-type and sustained outward rectifier K+ currents. Compared to control, both A-type and sustained K+ current densities were significantly reduced (42 and 34%, respectively; P < 0.05) in labelled neurons from the inflamed intestine but not in non-labelled neurons. A-type current voltage dependence of inactivation was negatively shifted in labelled inflamed intestine neurons. Neurons also exhibited tetrodotoxin-sensitive and resistant Na+ currents. Tetrodotoxin-resistant sodium currents were increased by 37% in labelled neurons from the inflamed intestine compared to control (P < 0.01), whereas unlabelled neurons were unaffected. The activation and inactivation curves of these currents were unchanged by inflammation. These data suggest ileitis increases excitability of intestinal sensory neurons by modulating multiple ionic channels. The lack of effect in non-labelled neurons suggests signalling originated at the nerve terminal rather than through circulating mediators and, given that Na+ currents are enhanced whereas K+ currents are suppressed, one or more signalling pathways may be involved.

• Authors: Timothy Stewart, Michael J Beyak, Stephen Vanner
• Journal: The Journal of physiology (J Physiol) Vol. 552 Issue Pt 3 Pg. 797-807 (Nov 01 2003) ISSN: 0022-3751 [Print] England
• PMID: 12923214 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Potassium Channels
• Potassium Channels, Voltage-Gated
• Sodium Channels
• Tetrodotoxin
• Trinitrobenzenesulfonic Acid

Topics

• Animals
• Drug Resistance
• Electric Conductivity
• Female
• Ganglia, Spinal (physiopathology)
• Guinea Pigs
• Ileitis (chemically induced, physiopathology)
• Ion Channel Gating
• Male
• Models, Biological
• Neurons, Afferent
• Potassium Channels (metabolism)
• Potassium Channels, Voltage-Gated (metabolism)
• Sodium Channels (drug effects, metabolism)
• Tetrodotoxin (pharmacology)
• Trinitrobenzenesulfonic Acid