title: The Involvement of Ca(2+) Signal Pathways in Distal Colonic Myocytes in a Rat Model of Dextran Sulfate Sodium-induced Colitis.
abstract: BACKGROUND
  Disrupted Ca2+ 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) Ca2+ signaling and Ca2+ 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 Ca2+ levels (n = 3 in each group) and Ca2+ transients (n = 3 in each group) were measured in single colonic SM cells. Ca2+ 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 Ca2+ transients were observed in more SM cells from DSS-treated rats (15/30 cells) than from controls (5/36 cells). Peak caffeine-induced intracellular Ca2+ 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 Ca2+ 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 Ca2+ signaling of colonic SM, caused by alteration of Ca2+ handing proteins, contribute to colonic dysmotility in DSS-induced UC.
authors.affiliation: Department of Gastroenterology, Peking University First Hospital, Peking University, Beijing 100034, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Peking University First Hospital, Peking University, Beijing 100034, China.
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Li
authors.affiliation: Department of Biomacromolecules, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Guang-Ju
authors.initials: GJ
authors.lastname: Ji
authors.affiliation: Department of Biomacromolecules, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Zhai
authors.affiliation: Department of Gastroenterology, Peking University First Hospital, Peking University, Beijing 100034, China.
authors.forename: Hua-Hong
authors.initials: HH
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Peking University First Hospital, Peking University, Beijing 100034, China.
authors.forename: Xin-Guang
authors.initials: XG
authors.lastname: Liu
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000378:metabolism*; D003106:Colon / Q000166:cytology* / Q000378:metabolism*; D016264:Dextran Sulfate / Q000633:toxicity*; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016264:Dextran Sulfate