Enhanced excitability and down-regulated voltage-gated potassium channels in colonic DRG neurons from neonatal maternal separation rats

Jia Lie Luo, Hong Yan Qin, Chun Kit Wong, Suk Ying Tsang, Yu Huang, Zhaoxiang BIAN*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

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 (IA) and delayed rectifier (IK) K+ currents. Compared with NH rat neurons, the averaged density of IK 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 IK 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.

Original languageEnglish
Pages (from-to)600-609
Number of pages10
JournalJournal of Pain
Volume12
Issue number5
DOIs
Publication statusPublished - May 2011

Scopus Subject Areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

User-Defined Keywords

  • dorsal root ganglia
  • hyperexcitability
  • Neonatal maternal separation
  • visceral pain
  • voltage-gated K channel

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