Increased colonic motility in a rat model of irritable bowel syndrome is associated with up‐regulation of L‐type calcium channels in colonic smooth muscle cells

Objective This paper aimed to investigate the relationship between up‐regulation of L‐type calcium channels and altered motility disorder in a rat model of irritable bowel syndrome (IBS). Methods Male Sprague–Dawley rats were subjected to neonatal maternal separation (NMS) from postnatal day 2–14 or normal handling (NH), and used when weighted 250–300 g. Colonic smooth muscle contractions was studied in an organ bath system. L‐type Ca²⁺ channel α_1c subunit expression in smooth muscles from rat colon were studied by immunofluorescence and Western blotting analysis. The intracellular calcium concentration ([Ca²⁺]_i) of enzymatically isolated single colonic smooth muscle cell was studied with laser confocal fluorescent microscopy. Results The fecal pellets during 1 h water avoidance stress (WAS) were significantly increased; the amplitude of spontaneous contractions and contractions induced by Bay K 8644 (10 nm –1 μm ), KCl (10–60 mm ) and ACh (100 nm –10 μm ) were significantly increased in NMS rats, when comparing with that of NH rats. [Ca²⁺]i induced by Bay K 8644 (1 μm ), KCl (40 mm ), and ACh (10 μm ) significantly increased in muscle cells of NMS rats than NH rats. Further, α_1c protein expression was significantly up‐regulated in colonic smooth muscle of NMS rats than NH rats. Conclusion These results suggest that NMS lead to up‐regulation of L‐type Ca²⁺ channels expression in the colon, which contributes to the colonic motility disorder. Our findings provide direct evidence to help understanding the underlying mechanism of chronic stress‐induced colonic motility disorder in IBS.