title: Functional expression of large-conductance calcium-activated potassium channels in human endometrium: a novel mechanism involved in endometrial receptivity and embryo implantation.
abstract: BACKGROUND
  Large-conductance calcium-activated potassium channels (BK(Ca) channels) mediate physiological processes in nonexcitable cells.
  
  
  OBJECTIVE
  The aim of the study was to determine BK(Ca) channel expression in human endometrium and its role in endometrial receptivity and embryo implantation.
  
  
  METHODS
  BK(Ca) channel expression in human endometrium is described at different phases of the menstrual cycle using quantitative real time-PCR and Western blot techniques. Their effects on embryo implantation were examined using JAr spheroid attachment assays and in vivo mouse model. We examined their effects on endometrial receptivity factors, nuclear factor-κB (NF-κB) activity using quantitative real time-PCR, Western blot, and EMSA analyses. Changes in electrophysiological properties and cytosolic free Ca(2+) were measured in endometrial cells with or without specific BK(Ca) blocker or transfected with BK(Ca) small interfering RNA using patch-clamp and fluorescence analyses, respectively.
  
  
  RESULTS
  BK(Ca) channels are expressed in human endometrial cells in a phase-related fashion during the menstrual cycle (proliferative, 0.20 ± 0.02, vs. mid-secretory, 0.72 ± 0.07; P < 0.01). Blocking BK(Ca) channel function or knockdown of endogenous BK(Ca) channel expression not only decreased JAr spheroid attachment rate and embryo implantation rate in mice but also significantly reduced the expression levels of endometrial receptive factors, including leukemia inhibitory factor, integrin β3, claudin-4, and DKK-1, in human endometrial cells. Blocking BK(Ca) channels also reduced BK(Ca)-regulated NF-κB activity, cytosolic Ca(2+) concentrations, and membrane potentials in human endometrial cells.
  
  
  CONCLUSIONS
  These observations demonstrate that BK(Ca) channels: 1) are expressed in endometrial cells; 2) affect embryo implantation by mediating endometrial receptive factors; and 3) alter the activity of NF-κB and homeostasis of Ca(2+) in the human endometrial cells.
authors.affiliation: Department of Reproductive Endocrinology, Key Laboratory of Reproductive Genetics, Ministry of Education, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China.
authors.forename: Run-Ju
authors.initials: RJ
authors.lastname: Zhang
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Zou
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Tan
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Wang
authors.forename: Ai-Xia
authors.initials: AX
authors.lastname: Liu
authors.forename: Fan
authors.initials: F
authors.lastname: Qu
authors.forename: Ye
authors.initials: Y
authors.lastname: Meng
authors.forename: Guo-Lian
authors.initials: GL
authors.lastname: Ding
authors.forename: Yong-Chao
authors.initials: YC
authors.lastname: Lu
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Lv
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Sheng
authors.forename: He-Feng
authors.initials: HF
authors.lastname: Huang
mesh_terms: D000328:Adult; D000818:Animals; D001706:Biopsy; D002478:Cells, Cultured; D010064:Embryo Implantation / Q000235:genetics* / Q000502:physiology; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008597:Menstrual Cycle / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051379:Mice; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D034741:RNA, Small Interfering