The Involvement of Ca(2+) Signal Pathways in Distal Colonic Myocytes in a Rat Model of Dextran Sulfate Sodium-induced Colitis

BACKGROUND: Disrupted Ca(2+) homeostasis contributes to the development of colonic dysmotility in ulcerative colitis (UC), but the underlying mechanisms are unknown. This study aimed to examine the alteration of colonic smooth muscle (SM) Ca(2+) signaling and Ca(2+) handling proteins in a rat model of dextran sulfate sodium (DSS)-induced UC. METHODS: Male Sprague-Dawley rats were randomly divided into control (n = 18) and DSS (n = 17) groups. Acute colitis was induced by 5% DSS in the drinking water for 7 days. Contractility of colonic SM strips (controls, n = 8 and DSS, n = 7) was measured in an organ bath. Cytosolic resting Ca(2+) levels (n = 3 in each group) and Ca(2+) transients (n = 3 in each group) were measured in single colonic SM cells. Ca(2+) handling protein expression was determined by Western blotting (n = 4 in each group). Differences between control and DSS groups were analyzed by a two-sample independent t-test. RESULTS: Average tension and amplitude of spontaneous contractions of colonic muscle strips were significantly enhanced in DSS-treated rats compared with controls (1.25 ± 0.08 g vs. 0.96 ± 0.05 g, P = 0.007; and 2.67 ± 0.62 g vs. 0.52 ± 0.10 g, P = 0.013). Average tensions of carbachol-evoked contractions were much weaker in the DSS group (1.08 ± 0.10 g vs. 1.80 ± 0.19 g, P = 0.006). Spontaneous Ca(2+) transients were observed in more SM cells from DSS-treated rats (15/30 cells) than from controls (5/36 cells). Peak caffeine-induced intracellular Ca(2+) release was lower in SM cells of DSS-treated rats than controls (0.413 ± 0.046 vs. 0.548 ± 0.041, P = 0.033). Finally, several Ca(2+) handling proteins in colonic SM were altered by DSS treatment, including sarcoplasmic reticulum calcium-transporting ATPase 2a downregulation and phospholamban and inositol 1,4,5-trisphosphate receptor 1 upregulation. CONCLUSIONS: Impaired intracellular Ca(2+) signaling of colonic SM, caused by alteration of Ca(2+) handing proteins, contribute to colonic dysmotility in DSS-induced UC.