Abstract
Cardiac fibroblasts are an integral part of the myocardial tissue and contribute to its remodelling. This study characterizes for the first time the calcium-dependent chloride channels (CaCC) in the plasma membrane of primary human atrial cardiac fibroblasts by means of iodide efflux and patch clamp methods. The calcium ionophore A23187 and Angiotensin II (AgII) 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 of anoctamine 1 (ANO1) but not by Anoctamine 2 (ANO2) which have been revealed as CaCC. The effect of AgII on anion efflux is mediated through AT1 receptors (with an EC50 = 13.8 ± 1.3 nM). Blockade of anion efflux by calphostin C suggests that chloride conductance activation is dependent on PKC. We conclude that ANO1 carries CaCC current in human cardiac fibroblasts and that this is regulated by AgII acting via the AT1 receptor pathway.
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