title: Estrogen regulates the expression of small-conductance Ca-activated K+ channels in colonic smooth muscle cells.
abstract: OBJECTIVE
  This study aimed to determine the effects of small-conductance Ca(2+)-activated K(+) (SK) channels in colonic relaxation and the regulation of SK channels by estrogen.
  
  
  METHODS
  The contractile activity of muscle strips from male rats was estimated, and drugs including vehicle (DMSO), 17β-estradiol (E2), or apamin (SK blocker) were added, respectively. In a further experiment, muscle strips were preincubated with apamin before exposure to E2. The levels of the SK2 and SK3 protein expression in the colonic smooth muscle cells (SMCs) were detected. SMCs were treated with ICI 182780 (estrogen receptor [ER] antagonist) plus E2, BSA-E2, PPT (ERα agonist), or DPN (ERβ agonist). SK3 mRNA and protein expression levels were detected.
  
  
  RESULTS
  The muscle strips responded to E2 with a decrease and to apamin with a transient increase in tension. Preincubation with apamin partially prevented E2-induced relaxation. Two SK channel subtypes, SK2 and SK3, were coexpressed with α-actin in colonic SMCs. The quantitative ratio of the SK transcriptional expression in colonic SMCs was SK3 > SK2. The SK3 expression was upregulated by E2, and was downregulated by ICI 182780, but was not influenced by BSA-E2. Furthermore, the effect of PPT on the expression of SK3 was almost the same as that of E2, while DPN did not influence the protein expression of SK3.
  
  
  CONCLUSIONS
  These findings indicate that SK3 is involved in the E2-induced relaxing effect on rat colonic smooth muscle. Furthermore, E2 upregulates the expression of SK3 in rat SMCs, and that this effect is mediated via the ERα receptor.
authors: Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors: Yu-Rong
authors: YR
authors: Tang
authors: Wei-Wei
authors: WW
authors: Yang
authors: Yun
authors: Y
authors: Wang
authors: Yao-Yao
authors: YY
authors: Gong
authors: Liu-Qin
authors: LQ
authors: Jiang
authors: Lin
authors: L
authors: Lin
mesh_terms: D000199:Actins / Q000187:drug effects / Q000235:genetics; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000819:agonists / Q000494:pharmacology*; D000077267:Fulvestrant; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D000199:Actins; D065171:Estrogen Receptor Antagonists; D004967:Estrogens; C496898:Kcnn2 protein, mouse; C496900:Kcnn3 protein, mouse; D014677:Pharmaceutical Vehicles; D012333:RNA, Messenger; D051640:Small-Conductance Calcium-Activated Potassium Channels; C043090:estradiol-bovine serum albumin; D000077267:Fulvestrant; D001030:Apamin; D012710:Serum Albumin, Bovine; D004958:Estradiol; D002217:Carbachol; D004121:Dimethyl Sulfoxide