title: ANO1 contributes to angiotensin-II-activated Ca2+-dependent Cl- current in human atrial fibroblasts.
abstract: Cardiac fibroblasts are an integral part of the myocardial tissue and contribute to its remodelling. This study characterises for the first time the calcium-dependent chloride channels (CaCC) in the plasma membrane of primary human atrial cardiac fibroblasts by means of the iodide efflux and the patch clamp methods. The calcium ionophore A23187 and Angiotensin II (Ang II) activate a chloride conductance in cardiac fibroblasts that shares pharmacological similarities with calcium-dependent chloride channels. This chloride conductance is depressed by RNAi-mediated selective Anoctamine 1 (ANO1) but not by Anoctamine 2 (ANO2) which has been revealed as CaCC and is inhibited by the selective ANO1 inhibitor, T16inh-A01. The effect of Ang II on anion efflux is mediated through AT1 receptors (with an EC50 = 13.8 ± 1.3 nM). The decrease of anion efflux by calphostin C and bisindolylmaleimide I (BIM I) suggests that chloride conductance activation is dependent on PKC. We conclude that ANO1 contributes to CaCC current in human cardiac fibroblasts and that this is regulated by Ang II acting via the AT1 receptor pathway.
authors.affiliation: ERL CNRS 7368, Université de Poitiers, 1 rue Georges Bonnet, 86022 Poitiers Cedex, France.
authors.forename: Antoun
authors.initials: A
authors.lastname: El Chemaly
authors.affiliation: ERL CNRS 7368, Université de Poitiers, 1 rue Georges Bonnet, 86022 Poitiers Cedex, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Norez
authors.affiliation: ERL CNRS 7368, Université de Poitiers, 1 rue Georges Bonnet, 86022 Poitiers Cedex, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Magaud
authors.affiliation: ERL CNRS 7368, Université de Poitiers, 1 rue Georges Bonnet, 86022 Poitiers Cedex, France.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Bescond
authors.affiliation: ERL CNRS 7368, Université de Poitiers, 1 rue Georges Bonnet, 86022 Poitiers Cedex, France.
authors.forename: Aurelien
authors.initials: A
authors.lastname: Chatelier
authors.affiliation: Laboratoire de Physiologie, Faculté de Médecine-PTS, USJ, Beyrouth, Liban.
authors.forename: Nassim
authors.initials: N
authors.lastname: Fares
authors.affiliation: ERL CNRS 7368, Faculté des Sciences, Université François Rabelais de Tours, 37200 Tours, France.
authors.forename: Ian
authors.initials: I
authors.lastname: Findlay
authors.affiliation: Service de chirurgie cardio-thoracique, CHU Poitiers, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Jayle
authors.affiliation: ERL CNRS 7368, Université de Poitiers, 1 rue Georges Bonnet, 86022 Poitiers Cedex, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Becq
authors.affiliation: ERL CNRS 7368, Université de Poitiers, 1 rue Georges Bonnet, 86022 Poitiers Cedex, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Faivre
authors.affiliation: ERL CNRS 7368, Université de Poitiers, 1 rue Georges Bonnet, 86022 Poitiers Cedex, France. Electronic address: patrick.bois@univ-poitiers.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bois
mesh_terms: D000368:Aged; D000804:Angiotensin II / Q000502:physiology*; D000075369:Anoctamin-1; D001692:Biological Transport; D020013:Calcium Signaling; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018118:Chloride Channels / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006325:Heart Atria / Q000166:cytology; D006801:Humans; D007700:Kinetics; D008297:Male; D009363:Neoplasm Proteins / Q000502:physiology*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D018118:Chloride Channels; D002712:Chlorides; D009363:Neoplasm Proteins; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II
keywords: ANO1; Angiotensin II; Calcium-dependent chloride channels; Human cardiac fibroblasts; TMEM16A