Article Dans Une Revue Pflügers Archiv European Journal of Physiology Année : 2020

TRPM4 non-selective cation channel in human atrial fibroblast growth

Racim Adjlane
Laurent Sallé

Résumé

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.

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Dates et versions

hal-03715736 , version 1 (06-07-2022)

Identifiants

Citer

Christophe Simard, Christophe Magaud, Racim Adjlane, Quentin Dupas, Laurent Sallé, et al.. TRPM4 non-selective cation channel in human atrial fibroblast growth. Pflügers Archiv European Journal of Physiology, 2020, 472 (12), pp.1719-1732. ⟨10.1007/s00424-020-02476-0⟩. ⟨hal-03715736⟩
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