title: Calcium-activated chloride channels anoctamin 1 and 2 promote murine uterine smooth muscle contractility.
abstract: OBJECTIVE
  To determine the presence of calcium activated chloride channels anoctamin 1 (ANO1) and 2 (ANO2) in human and murine uterine smooth muscle (MUSM) and evaluate the physiologic role for these ion channels in murine myometrial contractility.
  
  
  METHODS
  We performed reverse transcription polymerase chain reaction to determine whether ANO1 and 2 are expressed in human and murine uterine tissue to validate the study of this protein in mouse models. Immunohistochemical staining of ANO1 and 2 was then performed to determine protein expression in murine myometrial tissue. The function of ANO1 and 2 in murine uterine tissue was evaluated using electrophysiologic studies, organ bath, and calcium flux experiments.
  
  
  RESULTS
  ANO1 and 2 are expressed in human and MUSM cells. Functional studies show that selective antagonism of these channels promotes relaxation of spontaneous MUSM contractions. Blockade of ANO1 and 2 inhibits both agonist-induced and spontaneous transient inward currents and abolishes G-protein coupled receptor (oxytocin) mediated elevations in intracellular calcium.
  
  
  CONCLUSIONS
  The calcium activated chloride channels ANO1 and 2 are present in human and murine myometrial tissue and may provide novel potential therapeutic targets to achieve effective tocolysis.
authors.affiliation: Department of Anesthesiology, Columbia University College of Physicians and Surgeons, Columbia University Medical Center, New York, NY.
authors.forename: Kyra
authors.initials: K
authors.lastname: Bernstein
authors.affiliation: Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY.
authors.forename: Joy Y
authors.initials: JY
authors.lastname: Vink
authors.affiliation: Department of Anesthesiology, Columbia University College of Physicians and Surgeons, Columbia University Medical Center, New York, NY.
authors.forename: Xiao Wen
authors.initials: XW
authors.lastname: Fu
authors.affiliation: Department of Anesthesiology, Columbia University College of Physicians and Surgeons, Columbia University Medical Center, New York, NY.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Wakita
authors.affiliation: Department of Anesthesiology, Columbia University College of Physicians and Surgeons, Columbia University Medical Center, New York, NY.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Danielsson
authors.affiliation: Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY.
authors.forename: Ronald
authors.initials: R
authors.lastname: Wapner
authors.affiliation: Department of Anesthesiology, Columbia University College of Physicians and Surgeons, Columbia University Medical Center, New York, NY. Electronic address: gg2125@columbia.edu.
authors.forename: George
authors.initials: G
authors.lastname: Gallos
mesh_terms: D000818:Animals; D000075369:Anoctamin-1; D000075368:Anoctamins; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009126:Muscle Relaxation / Q000502:physiology; D009215:Myometrium / Q000378:metabolism* / Q000502:physiology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014590:Uterine Contraction / Q000378:metabolism* / Q000502:physiology
chemical_list: C476213:ANO1 protein, human; C531181:ANO1 protein, mouse; C521849:ANO2 protein, human; C532161:ANO2 protein, mouse; D000075369:Anoctamin-1; D000075368:Anoctamins; D018118:Chloride Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D002118:Calcium
keywords: anoctamin; calcium channels; contractility; myometrium; uterus