TRPM4 non-selective cation channel in human atrial fibroblast growth
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ION CHANNELS, RECEPTORS AND TRANSPORTERS
TRPM4 non-selective cation channel in human atrial fibroblast growth Christophe Simard 1 & Christophe Magaud 2 & Racim Adjlane 1 & Quentin Dupas 1 Alain Manrique 1 & Patrick Bois 2 & Jean-François Faivre 2 & Romain Guinamard 1
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Laurent Sallé 1
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Received: 22 April 2020 / Revised: 30 September 2020 / Accepted: 6 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Cardiac fibroblasts play an important role in cardiac matrix turnover and are involved in cardiac fibrosis development. Ca2+ is a driving belt in this phenomenon. This study evaluates the functional expression and contribution of the Ca2+-activated channel TRPM4 in atrial fibroblast phenotype. Molecular and electrophysiological investigations were conducted in human atrial fibroblasts in primary culture and in atrial fibroblasts obtained from wild-type and transgenic mice with disrupted Trpm4 gene (Trpm4−/−). A typical TRPM4 current was recorded on human cells (equal selectivity for Na+ and K+, activation by internal Ca2+, voltage sensitivity, conductance of 23.2 pS, inhibition by 9-phenanthrol (IC50 = 6.1 × 10−6 mol L−1)). Its detection rate was 13% on patches at days 2–4 in culture but raised to 100% on patches at day 28. By the same time, a cell growth was observed. This growth was smaller when cells were maintained in the presence of 9-phenanthrol. Similar cell growth was measured on wild-type mice atrial fibroblasts during culture. However, this growth was minimized on Trpm4−/− mice fibroblasts compared to control animals. In addition, the expression of alpha smooth muscle actin increased during culture of atrial fibroblasts from wild-type mice. This was not observed in Trpm4−/− mice fibroblasts. It is concluded that TRPM4 participates in fibroblast growth and could thus be involved in cardiac fibrosis. Keywords TRPM4 . Fibroblast . Atria . Fibrosis . Electrophysiology
Introduction Transient receptor potential melastatin 4 (TRPM4) is a nonselective cation channel widely expressed among mammalian tissues with a specific high expression in the heart [24, 38, 41]. In cardiac tissue, TRPM4 has been mainly evaluated for its contribution to cardiomyocytes and conductive tissue functions [26, 37]. It participates in electrical pacemaking in sinus node cells [10, 29] and action potentials in Purkinje fibers cells Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00424-020-02476-0) contains supplementary material, which is available to authorized users. * Romain Guinamard [email protected] 1
Groupe Signalisation, Electrophysiologie et Imagerie des Lésions d’Ischémie-Reperfusion Myocardique, EA4650, GIP Cyceron, Université de Caen Normandie, Sciences D, Esplanade de la Paix, 14032 Caen Cedex 5, France
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Laboratoire Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers, CNRS, Poitiers, France
[30] as well as in cardiomyocytes [11, 42, 53]. Note that it has been functionally recorded in freshly isolate
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