| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
NEUROREGULATION AND MOTILITY
1Gastrointestinal Diseases Research Unit and 2Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada K7L 5G2
Submitted 7 April 2004 ; accepted in final form 16 June 2004
The composition of Na+ currents in dorsal root ganglia (DRG) neurons depends on their neuronal phenotype and innervation target. Two TTX-resistant (TTX-R) Na+ currents [voltage-gated Na channels (Nav)] have been described in small DRG neurons; one with slow inactivation kinetics (Nav1.8) and the other with persistent kinetics (Nav1.9), and their modulation has been implicated in inflammatory pain. This has not been studied in neurons projecting to the colon. This study examined the relative importance of these currents in inflammation-induced changes in a mouse model of inflammatory bowel disease. Colonic sensory neurons were retrogradely labeled, and colitis was induced by instillation of trinitrobenzenesulfonic acid (TNBS) into the lumen of the distal colon. Seven to ten days later, immunohistochemical properties were characterized in controls, and whole cell recordings were obtained from small (<40 pF) labeled DRG neurons from control and TNBS animals. Most neurons exhibited both fast TTX-sensitive (TTX-S)- and slow TTX-R-inactivating Na+ currents, but persistent TTX-R currents were uncommon (<15%). Most labeled neurons were CGRP (79%), tyrosine kinase A (trkA) (84%) immunoreactive, but only a small minority bind IB4 (14%). TNBS-colitis caused ulceration, thickening of the colon and significantly increased neuronal excitability. The slow TTX-R-inactivating Na current density (Nav1.8) was significantly increased, but other Na currents were unaffected. Most small mouse colonic sensory neurons are CGRP, trkA immunoreactive, but not isolectin B4 reactive and exhibit fast TTX-S, slow TTX-R, but not persistent TTX-R Na+ currents. Colitis-induced hyperexcitability is associated with increased slow TTX-R (Nav1.8) Na+ current. Together, these findings suggest that colitis alters trkA-positive neurons to preferentially increase slow TTX-R Na+ (Nav1.8) currents.
tyrosine kinase A-positive neurons; sodium channels; nociception colon
This article has been cited by other articles:
|
|
 |
|
  D. R. Robinson and G. F. Gebhart Inside Information: The Unique Features of Visceral Sensation Mol. Interv., October 1, 2008; 8(5): 242 - 253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Lynn, B. N. Chen, V. P. Zagorodnyuk, M. Costa, and S. J. H. Brookes TNBS-induced inflammation modulates the function of one class of low-threshold rectal mechanoreceptors in the guinea pig Am J Physiol Gastrointest Liver Physiol, October 1, 2008; 295(4): G862 - G871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Gomez-Pinilla, P. J. Camello, and M. J. Pozo Effects of Melatonin on Gallbladder Neuromuscular Function in Acute Cholecystitis J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 138 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Nurgali, T. V. Nguyen, H. Matsuyama, M. Thacker, H. L. Robbins, and J. B. Furness Phenotypic changes of morphologically identified guinea-pig myenteric neurons following intestinal inflammation J. Physiol., September 1, 2007; 583(2): 593 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kayssi, S. Amadesi, F. Bautista, N. W. Bunnett, and S. Vanner Mechanisms of protease-activated receptor 2-evoked hyperexcitability of nociceptive neurons innervating the mouse colon J. Physiol., May 1, 2007; 580(3): 977 - 991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Coldwell, B. D. Phillis, K. Sutherland, G. S. Howarth, and L. A. Blackshaw Increased responsiveness of rat colonic splanchnic afferents to 5-HT after inflammation and recovery J. Physiol., February 15, 2007; 579(1): 203 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hillsley, J.-H. Lin, A. Stanisz, D. Grundy, J. Aerssens, P. J. Peeters, D. Moechars, B. Coulie, and R. H. Stead Dissecting the role of sodium currents in visceral sensory neurons in a model of chronic hyperexcitability using Nav1.8 and Nav1.9 null mice J. Physiol., October 1, 2006; 576(1): 257 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-Y. Xu, J. H. Winston, M. Shenoy, H. Yin, and P. J. Pasricha Enhanced excitability and suppression of A-type K+ current of pancreas-specific afferent neurons in a rat model of chronic pancreatitis Am J Physiol Gastrointest Liver Physiol, September 1, 2006; 291(3): G424 - G431. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Guagnini, M Valenti, S Mukenge, I Matias, A Bianchetti, S Di Palo, G Ferla, V Di Marzo, and T Croci Neural contractions in colonic strips from patients with diverticular disease: role of endocannabinoids and substance P Gut, July 1, 2006; 55(7): 946 - 953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Peeters, J. Aerssens, R. de Hoogt, A. Stanisz, H. W. Gohlmann, K. Hillsley, A. Meulemans, D. Grundy, R. H. Stead, and B. Coulie Molecular profiling of murine sensory neurons in the nodose and dorsal root ganglia labeled from the peritoneal cavity Physiol Genomics, February 23, 2006; 24(3): 252 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-Y. Huang and M. Hanani Morphological and electrophysiological changes in mouse dorsal root ganglia after partial colonic obstruction Am J Physiol Gastrointest Liver Physiol, October 1, 2005; 289(4): G670 - G678. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
