Down-regulation of A-type potassium channel in gastric-specific DRG neurons in a rat model of functional dyspepsia

S. Li, J. D.Z. Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Although without evidence of organic structural abnormalities, pain or discomfort is a prominent symptom of functional dyspepsia and considered to reflect visceral hypersensitivity whose underlying mechanism is poorly understood. Here, we studied electrophysiological properties and expression of voltage-gated potassium channels in dorsal root ganglion (DRG) neurons in a rat model of functional dyspepsia induced by neonatal gastric irritation. Methods: Male Sprague-Dawley rat pups at 10-day old received 0.1% iodoacetamide (IA) or vehicle by oral gavage for 6 days and studied at adulthood. Retrograde tracer-labeled gastric-specific T8-T12 DRG neurons were harvested for the patch-clamp study in voltage and current-clamp modes and protein expression of K+ channel in T8-T12 DRGs was examined by western blotting. Key Results: (1) Gastric specific but not non-gastric DRG neurons showed an enhanced excitability in neonatal IA-treated rats compared to the control: depolarized resting membrane potentials, a lower current threshold for action potential (AP) activation, and an increase in the number of APs in response to current stimulation. (2) The current density of tetraethylammonium insensitive (transiently inactivating A-type current), but not the tetraethylammonium sensitive (slow-inactivating delayed rectifier K+ currents), was significantly smaller in IA-treated rats (65.4 ± 6.9 pA/pF), compared to that of control (93.1 ± 8.3 pA/pF). (3) Protein expression of KV4.3 was down-regulated in IA-treated rats. Conclusions & Inferences: A-type potassium channels are significantly down-regulated in the gastric-specific DRG neurons in adult rats with mild neonatal gastric irritation, which in part contribute to the enhanced DRG neuron excitabilities that leads to the development of gastric hypersensitivity.

Original languageEnglish (US)
Pages (from-to)962-970
Number of pages9
JournalNeurogastroenterology and Motility
Volume26
Issue number7
DOIs
StatePublished - Jul 2014

Keywords

  • Dorsal root ganglion
  • Functional dyspepsia
  • Gastric
  • Potassium channel
  • Visceral pain
  • Voltage gated

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

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