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Enhanced excitability and down-regulated voltage-gated potassium channels in colonic drg neurons from neonatal maternal separation rats.
J Pain. 2011 May; 12(5):600-9.JP

Abstract

Irritable bowel syndrome (IBS), characterized mainly by abdominal pain, is a functional bowel disorder. The present study aimed to examine changes in the excitability and the activity of the voltage-gated K(+) channel in dorsal root ganglia (DRG) neurons innervating the colon of rats subjected to neonatal maternal separation (NMS). Colonic DRG neurons from NMS rats as identified by FAST DiI™ labeling showed an increased cell size compared with those from nonhandled (NH) rats. Whole cell current-clamp recordings showed that colonic DRG neurons from NMS rats displayed: 1) depolarized resting membrane potential; 2) increased input resistance; 3) a dramatic reduction in rheobase; and 4) a significant increase in the number of action potentials evoked at twice rheobase. Whole cell voltage-clamp recordings revealed that neurons from both groups exhibited transient A-type (I(A)) and delayed rectifier (I(K)) K(+) currents. Compared with NH rat neurons, the averaged density of I(K) was significantly reduced in NMS rat neurons. Furthermore, the Kv1.2 expression was significantly decreased in NMS rat colonic DRG neurons. These results suggest that NMS increases the excitability of colonic DRG neurons mainly by suppressing the I(K) current, which is likely accounted for by the downregulation of the Kv1.2 expression and somal hypertrophy.

PERSPECTIVE

This study demonstrates the alteration of delayed rectifier K current and Kv1.2 expression in DRG neurons from IBS model rats, representing a molecular mechanism underlying visceral pain and sensitization in IBS, suggesting the potential of Kv1.2 as a therapeutic target for the treatment of IBS.

Authors+Show Affiliations

School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.No 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

21296029

Citation

Luo, Jia-Lie, et al. "Enhanced Excitability and Down-regulated Voltage-gated Potassium Channels in Colonic Drg Neurons From Neonatal Maternal Separation Rats." The Journal of Pain : Official Journal of the American Pain Society, vol. 12, no. 5, 2011, pp. 600-9.
Luo JL, Qin HY, Wong CK, et al. Enhanced excitability and down-regulated voltage-gated potassium channels in colonic drg neurons from neonatal maternal separation rats. J Pain. 2011;12(5):600-9.
Luo, J. L., Qin, H. Y., Wong, C. K., Tsang, S. Y., Huang, Y., & Bian, Z. X. (2011). Enhanced excitability and down-regulated voltage-gated potassium channels in colonic drg neurons from neonatal maternal separation rats. The Journal of Pain : Official Journal of the American Pain Society, 12(5), 600-9. https://doi.org/10.1016/j.jpain.2010.11.005
Luo JL, et al. Enhanced Excitability and Down-regulated Voltage-gated Potassium Channels in Colonic Drg Neurons From Neonatal Maternal Separation Rats. J Pain. 2011;12(5):600-9. PubMed PMID: 21296029.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced excitability and down-regulated voltage-gated potassium channels in colonic drg neurons from neonatal maternal separation rats. AU - Luo,Jia-Lie, AU - Qin,Hong-Yan, AU - Wong,Chun-Kit, AU - Tsang,Suk-Ying, AU - Huang,Yu, AU - Bian,Zhao-Xiang, Y1 - 2011/02/05/ PY - 2010/05/19/received PY - 2010/10/26/revised PY - 2010/11/23/accepted PY - 2011/2/8/entrez PY - 2011/2/8/pubmed PY - 2011/9/13/medline SP - 600 EP - 9 JF - The journal of pain : official journal of the American Pain Society JO - J Pain VL - 12 IS - 5 N2 - UNLABELLED: Irritable bowel syndrome (IBS), characterized mainly by abdominal pain, is a functional bowel disorder. The present study aimed to examine changes in the excitability and the activity of the voltage-gated K(+) channel in dorsal root ganglia (DRG) neurons innervating the colon of rats subjected to neonatal maternal separation (NMS). Colonic DRG neurons from NMS rats as identified by FAST DiI™ labeling showed an increased cell size compared with those from nonhandled (NH) rats. Whole cell current-clamp recordings showed that colonic DRG neurons from NMS rats displayed: 1) depolarized resting membrane potential; 2) increased input resistance; 3) a dramatic reduction in rheobase; and 4) a significant increase in the number of action potentials evoked at twice rheobase. Whole cell voltage-clamp recordings revealed that neurons from both groups exhibited transient A-type (I(A)) and delayed rectifier (I(K)) K(+) currents. Compared with NH rat neurons, the averaged density of I(K) was significantly reduced in NMS rat neurons. Furthermore, the Kv1.2 expression was significantly decreased in NMS rat colonic DRG neurons. These results suggest that NMS increases the excitability of colonic DRG neurons mainly by suppressing the I(K) current, which is likely accounted for by the downregulation of the Kv1.2 expression and somal hypertrophy. PERSPECTIVE: This study demonstrates the alteration of delayed rectifier K current and Kv1.2 expression in DRG neurons from IBS model rats, representing a molecular mechanism underlying visceral pain and sensitization in IBS, suggesting the potential of Kv1.2 as a therapeutic target for the treatment of IBS. SN - 1528-8447 UR - https://www.unboundmedicine.com/medline/citation/21296029/Enhanced_excitability_and_down_regulated_voltage_gated_potassium_channels_in_colonic_drg_neurons_from_neonatal_maternal_separation_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1526-5900(10)00830-8 DB - PRIME DP - Unbound Medicine ER -