ANO1 contributes to angiotensin-II-activated Ca2+-dependent Cl- current in human atrial fibroblasts. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Molecular and Cellular Cardiology Année : 2014

ANO1 contributes to angiotensin-II-activated Ca2+-dependent Cl- current in human atrial fibroblasts.

Résumé

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.
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Dates et versions

hal-00990329 , version 1 (13-05-2014)

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Antoun El Chemaly, Caroline Norez, Christophe Magaud, Jocelyn Bescond, Aurelien Chatelier, et al.. ANO1 contributes to angiotensin-II-activated Ca2+-dependent Cl- current in human atrial fibroblasts.. Journal of Molecular and Cellular Cardiology, 2014, 68, pp.12-9. ⟨10.1016/j.yjmcc.2013.12.027⟩. ⟨hal-00990329⟩
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