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Voltage-gated potassium channels in IB4-positive colonic sensory neurons mediate visceral hypersensitivity in the rat.
Am J Gastroenterol. 2009 Aug; 104(8):2014-27.AJ

Abstract

OBJECTIVES

Irritable bowel syndrome (IBS) is associated with a state of chronic visceral hypersensitivity, but the underlying molecular mechanisms of visceral hyperalgesia remain elusive. This study was designed to examine changes in the excitability and alterations of voltage-gated K+ currents in subpopulations of colonic dorsal root ganglion (DRG) neurons in a rat model of IBS-like visceral hypersensitivity.

METHODS

The model of IBS-like visceral hypersensitivity was induced by intracolonic infusion of 0.5% acetic acid (AA) in saline from postnatal days 8 -21. Experiments were conducted when rats became adults. DRG neurons innervating the colon were identified by 1,1'-dioleoyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate (DiI) fluorescence labeling and were immunostained for isolectin B4 (IB4) binding to classify these colonic neurons. Patch-clamp recordings were made from acutely dissociated DiI-labeled DRG neurons, and the expression of K+ channel in L6-S2 DRG was examined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot.

RESULTS

(1) Neonatal AA treatment induced long-lasting visceral hypersensitivity without significant inflammation but with mast cell hyperplasia. (2) Colonic DRG neurons contained IB4-positive and negative neurons with different electrophysiological properties. IB4-positive colonic neurons have longer action potentials (APs) and larger A-type K+ currents (I(A)) than the IB4-negative neurons, and IB4 phenotypic changes of colonic neurons were not involved in the chronic visceral hypersensitivity. (3) Neonatal AA treatment decreased I(A) density and changed the electrophysiological properties of I(A) and I(K) by shifting the steady-state inactivation toward a negative direction in IB4-positive colonic neurons. The excitability of these cells increased. (4) Kv4.3 was downregulated in neonatal AA-treated rats compared with control rats, which suggests a possible mechanism regarding the changes in electrical activity of DRG neurons in these rats.

CONCLUSIONS

A new model for chronic visceral hypersensitivity following a diluted AA stimulus in the neonatal period is described. The hypersensitivity may be associated with mast cell hyperplasia in the colon and increased excitability of IB4-positive colonic neurons as a result of suppression of I(A) density and a shift in the inactivation curves of I(A) and I(K) in a hyperpolarizing direction in these cells. This study identifies for the first time a specific molecular mechanism in subpopulations of colonic DRG neurons that underlies chronic visceral hypersensitivity.

Authors+Show Affiliations

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19491827

Citation

Qian, Ai-Hua, et al. "Voltage-gated Potassium Channels in IB4-positive Colonic Sensory Neurons Mediate Visceral Hypersensitivity in the Rat." The American Journal of Gastroenterology, vol. 104, no. 8, 2009, pp. 2014-27.
Qian AH, Liu XQ, Yao WY, et al. Voltage-gated potassium channels in IB4-positive colonic sensory neurons mediate visceral hypersensitivity in the rat. Am J Gastroenterol. 2009;104(8):2014-27.
Qian, A. H., Liu, X. Q., Yao, W. Y., Wang, H. Y., Sun, J., Zhou, L., & Yuan, Y. Z. (2009). Voltage-gated potassium channels in IB4-positive colonic sensory neurons mediate visceral hypersensitivity in the rat. The American Journal of Gastroenterology, 104(8), 2014-27. https://doi.org/10.1038/ajg.2009.227
Qian AH, et al. Voltage-gated Potassium Channels in IB4-positive Colonic Sensory Neurons Mediate Visceral Hypersensitivity in the Rat. Am J Gastroenterol. 2009;104(8):2014-27. PubMed PMID: 19491827.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Voltage-gated potassium channels in IB4-positive colonic sensory neurons mediate visceral hypersensitivity in the rat. AU - Qian,Ai-Hua, AU - Liu,Xin-Qiu, AU - Yao,Wei-Yan, AU - Wang,Hong-Yu, AU - Sun,Jing, AU - Zhou,Lin, AU - Yuan,Yao-Zong, Y1 - 2009/06/02/ PY - 2009/6/4/entrez PY - 2009/6/6/pubmed PY - 2009/8/21/medline SP - 2014 EP - 27 JF - The American journal of gastroenterology JO - Am J Gastroenterol VL - 104 IS - 8 N2 - OBJECTIVES: Irritable bowel syndrome (IBS) is associated with a state of chronic visceral hypersensitivity, but the underlying molecular mechanisms of visceral hyperalgesia remain elusive. This study was designed to examine changes in the excitability and alterations of voltage-gated K+ currents in subpopulations of colonic dorsal root ganglion (DRG) neurons in a rat model of IBS-like visceral hypersensitivity. METHODS: The model of IBS-like visceral hypersensitivity was induced by intracolonic infusion of 0.5% acetic acid (AA) in saline from postnatal days 8 -21. Experiments were conducted when rats became adults. DRG neurons innervating the colon were identified by 1,1'-dioleoyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate (DiI) fluorescence labeling and were immunostained for isolectin B4 (IB4) binding to classify these colonic neurons. Patch-clamp recordings were made from acutely dissociated DiI-labeled DRG neurons, and the expression of K+ channel in L6-S2 DRG was examined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. RESULTS: (1) Neonatal AA treatment induced long-lasting visceral hypersensitivity without significant inflammation but with mast cell hyperplasia. (2) Colonic DRG neurons contained IB4-positive and negative neurons with different electrophysiological properties. IB4-positive colonic neurons have longer action potentials (APs) and larger A-type K+ currents (I(A)) than the IB4-negative neurons, and IB4 phenotypic changes of colonic neurons were not involved in the chronic visceral hypersensitivity. (3) Neonatal AA treatment decreased I(A) density and changed the electrophysiological properties of I(A) and I(K) by shifting the steady-state inactivation toward a negative direction in IB4-positive colonic neurons. The excitability of these cells increased. (4) Kv4.3 was downregulated in neonatal AA-treated rats compared with control rats, which suggests a possible mechanism regarding the changes in electrical activity of DRG neurons in these rats. CONCLUSIONS: A new model for chronic visceral hypersensitivity following a diluted AA stimulus in the neonatal period is described. The hypersensitivity may be associated with mast cell hyperplasia in the colon and increased excitability of IB4-positive colonic neurons as a result of suppression of I(A) density and a shift in the inactivation curves of I(A) and I(K) in a hyperpolarizing direction in these cells. This study identifies for the first time a specific molecular mechanism in subpopulations of colonic DRG neurons that underlies chronic visceral hypersensitivity. SN - 1572-0241 UR - https://www.unboundmedicine.com/medline/citation/19491827/Voltage_gated_potassium_channels_in_IB4_positive_colonic_sensory_neurons_mediate_visceral_hypersensitivity_in_the_rat_ L2 - https://Insights.ovid.com/pubmed?pmid=19491827 DB - PRIME DP - Unbound Medicine ER -