Timothy Stewart and Michael J. Beyak contributed equally to this work.
Ileitis modulates potassium and sodium currents in guinea pig dorsal root ganglia sensory neurons
Article first published online: 16 JUL 2004
The Journal of Physiology
Volume 552, Issue 3, pages 797–807, November 2003
How to Cite
Stewart, T., Beyak, M. J. and Vanner, S. (2003), Ileitis modulates potassium and sodium currents in guinea pig dorsal root ganglia sensory neurons. The Journal of Physiology, 552: 797–807. doi: 10.1113/jphysiol.2003.046409
- Issue published online: 16 JUL 2004
- Article first published online: 16 JUL 2004
- (Received 7 May 2003; accepted after revision 12 August 2003; first published online 15 August 2003)
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.