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Applications of Spatio-temporal Mapping and Particle Analysis Techniques to Quantify Intracellular Ca2+ Signaling In Situ
Published on: January 7, 2019
Changes in membrane cholesterol affect caveolin-1 localization and ICC-pacing in mouse jejunum
E E Daniel1, Gregory Bodie, Marco Mannarino
1Department of Pharmacology, University of Alberta, Rm. 9-10, Medical Sciences Bldg., Edmonton, Alberta T6G 2H7, Canada. edaniel@ualberta.ca
American Journal of Physiology. Gastrointestinal and Liver Physiology
|February 24, 2004
Summary
Disrupting caveolae in mouse intestines with cholesterol modifiers (CD/WSC) altered pacing by interstitial cells of Cajal (ICC-MP). These changes suggest caveolae signaling plays a role in gut pacing.
Area of Science:
- Gastroenterology
- Cell Biology
- Physiology
Background:
- Intestinal pacing relies on interstitial cells of Cajal in the myenteric plexus (ICC-MP).
- Caveolae, plasma membrane invaginations rich in caveolins, act as signaling hubs.
- Caveolins modulate signaling protein activity within caveolae.
Purpose of the Study:
- To investigate the role of caveolae and caveolins in ICC-MP pacing.
- To determine if caveolae disruption affects intestinal smooth muscle contractions.
- To assess the specificity of caveolae modulation on cholinergic responses.
Main Methods:
- Treatment of intestinal segments with methyl beta-clodextrin (CD) to deplete cholesterol and water-soluble cholesterol (WSC) to load cholesterol.
- Measurement of pacing frequencies and paced contractions.
- Assessment of responses to carbamoyl choline and cholinergic nerve stimulation.
- Immunochemical and ultrastructural analysis of caveolin 1 and caveolae.
Main Results:
- Both CD and WSC treatments reduced pacing frequencies, with effects reversed by the other agent.
- Paced contractions were inhibited, but reversal was incomplete.
- CD depleted caveolin 1 and caveolae; WSC altered caveolin 1 distribution but not caveolae number.
- Neither treatment affected responses to exogenous or nerve-stimulated acetylcholine.
Conclusions:
- Caveolae signaling in ICC-MP is implicated in intestinal pacing.
- Caveolae modulation does not influence cholinergic neurotransmission in the intestine.
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