CO2 chemosensing in rat oesophagus
1Department of Medicine, School of Medicine, Los Angeles, California, USA.
Gut
|August 7, 2008
Summary
Carbon dioxide (CO2), not acid, may trigger heartburn by permeating the esophagus and activating nerve sensors. Inhibitors of carbonic anhydrase (CA), TRPV1, and ASICs block this CO2-induced response.
Area of Science:
- Gastroenterology
- Neuroscience
- Physiology
Background:
- Heartburn is commonly perceived as a sensation caused by esophageal acid.
- A hypothesis suggests that luminal carbon dioxide (CO2), a permeable gas, may be responsible for triggering this sensation instead of hydrogen ions (H+).
- This CO2 is proposed to permeate the esophageal epithelium and convert to H+, activating afferent neural signals via chemosensors.
Purpose of the Study:
- To investigate the role of luminal CO2 in esophageal afferent signaling.
- To determine if CO2, rather than H+, is the primary trigger for heartburn sensation.
- To identify the specific molecular mechanisms and sensors involved in CO2-induced esophageal responses.
Main Methods:
- Rat lower esophageal mucosa was superfused with various solutions, including high CO2 buffers and inhibitors of carbonic anhydrase (CA), TRPV1, and acid-sensing ion channels (ASICs).
- Interstitial pH and blood flow were measured to assess the physiological response.
- Immunohistochemistry was used to determine the expression patterns of CA, TRPV1, and ASICs in esophageal tissues.
Main Results:
- High CO2 perfusion induced hyperemia (increased blood flow) without altering interstitial pH, similar to acid perfusion.
- Inhibitors of CA (methazolamide, benzolamide), TRPV1 (capsazepine), and ASICs (amiloride) significantly inhibited the CO2-induced hyperemia.
- Specific carbonic anhydrase (CA XIV, CA XII), TRPV1, and ASIC (including ASIC3) expressions were identified in different layers and cell types of the esophageal epithelium and submucosa.
Conclusions:
- Luminal CO2 permeates the esophageal epithelium and activates TRPV1 and ASICs, leading to afferent neural signaling.
- Carbonic anhydrase enzymes play a crucial role in transducing the CO2 signal.
- Transepithelial CO2 permeation and subsequent activation of these chemosensors provide a plausible mechanism for the rapid transduction of luminal acid equivalents and the sensation of heartburn.
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