J Neurogastroenterol Motil.  2019 Oct;25(4):589-601. 10.5056/jnm19136.

Colonic Dysmotility in Murine Partial Colonic Obstruction Due to Functional Changes in Interstitial Cells

• Wang Q
• Zang J
• Huang X
• Lu H
• Xu W
• Chen J

• KMID: 2460488
• DOI: http://doi.org/10.5056/jnm19136

Abstract

BACKGROUND/AIMS
Interstitial cells play important roles in gastrointestinal (GI) neuro-smooth muscle transmission. The underlying mechanisms of colonic dysmotility have not been well illustrated. We established a partial colon obstruction (PCO) mouse model to investigate the changes of interstitial cells and the correlation with colonic motility.
METHODS
Western blot technique was employed to observe the protein expressions of Kit, platelet-derived growth factor receptor-α (Pdgfra), Ca²âº-activated Cl⁻ (Ano1) channels, and small conductance Ca²âº- activated K⁺ (SK) channels. Colonic migrating motor complexes (CMMCs) and isometric force measurements were employed in control mice and PCO mice.
RESULTS
PCO mice showed distended abdomen and feces excretion was significantly reduced. Anatomically, the colon above the obstructive silicone ring was obviously dilated. Kit and Ano1 proteins in the colonic smooth muscle layer of the PCO colons were significantly decreased, while the expression of Pdgfra and SK3 proteins were significantly increased. The effects of a nitric oxide synthase inhibitor (L-NAME) and an Ano1 channel inhibitor (NPPB) on CMMC and colonic spontaneous contractions were decreased in the proximal and distal colons of PCO mice. The SK agonist, CyPPA and antagonist, apamin in PCO mice showed more effect to the CMMCs and colonic smooth muscle contractions.
CONCLUSIONS
Colonic transit disorder may be due to the downregulation of the Kit and Ano1 channels and the upregulation of SK3 channels in platelet-derived growth factor receptor-α positive (PDGFRα⁺) cells. The imbalance between interstitial cells of Cajal-Ano1 and PDGFRα-SK3 distribution might be a potential reason for the colonic dysmotility.

Keyword

Chloride channels; Interstitial cells of Cajal; Small-conductance calcium-activated potassium channels

MeSH Terms

Abdomen
Animals
Apamin
Blotting, Western
Chloride Channels
Colon*
Down-Regulation
Feces
Interstitial Cells of Cajal
Mice
Muscle, Smooth
Myoelectric Complex, Migrating
Nitric Oxide Synthase
Platelet-Derived Growth Factor
Silicon
Silicones
Small-Conductance Calcium-Activated Potassium Channels
Up-Regulation
Apamin
Chloride Channels
Nitric Oxide Synthase
Platelet-Derived Growth Factor
Silicon
Silicones
Small-Conductance Calcium-Activated Potassium Channels