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Acid-sensing ion channels in gastrointestinal function.

Peter Holzer1

  • 1Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, A-8010 Graz, Austria.

Neuropharmacology
|January 14, 2015
PubMed
Summary
This summary is machine-generated.

Acid-sensing ion channels (ASICs) in the gut detect changes in acidity, contributing to pain and hypersensitivity in conditions like gastritis and irritable bowel syndrome. Targeting ASICs may offer new pain management strategies.

Keywords:
Acid surveillanceAcid-induced painAcid-related gastrointestinal diseasesAcid-sensing ion channelsGastrointestinal tractInflammationPrimary afferent neuronsProton-gated currentsVisceral hypersensitivity

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Area of Science:

  • Neuroscience
  • Gastroenterology
  • Physiology

Background:

  • Gastric acid is vital for digestion and pathogen defense but can damage the upper gastrointestinal mucosa, causing pain.
  • Luminal acidity in the colon is influenced by microbial activity and short-chain fatty acid production.
  • Acid-sensing ion channels (ASICs) and transient receptor potential ion channels are key sensors of pH in the gastrointestinal tract.

Purpose of the Study:

  • To investigate the role of ASICs in sensing acidity in the gastrointestinal tract.
  • To explore the involvement of ASICs in visceral hypersensitivity and pain.
  • To evaluate ASICs as potential therapeutic targets for functional gastrointestinal disorders.

Main Methods:

  • Expression analysis of ASICs (ASIC1, ASIC2, ASIC3) in vagal and spinal afferent neurons.
  • Electrophysiological studies to characterize proton-gated currents mediated by ASICs.
  • Experimental models to assess ASIC contribution to pain and hypersensitivity in gastrointestinal conditions.

Main Results:

  • ASICs are expressed in peripheral axons of afferent neurons in the gut.
  • ASICs mediate proton-gated currents and respond to decreases in extracellular pH.
  • ASICs contribute to gastric acid hypersensitivity and pain in gastritis and peptic ulceration.
  • ASICs are implicated in colonic hypersensitivity to distension in non-inflammatory conditions.

Conclusions:

  • ASICs play a significant role in sensing acidity and mediating pain in the gastrointestinal tract.
  • ASIC function is altered in inflammatory and non-inflammatory gastrointestinal pathologies.
  • ASICs represent promising therapeutic targets for managing visceral hypersensitivity and pain in functional gastrointestinal disorders.