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TRPM4 non-selective cation channel in human atrial fibroblast growth.

Authors
  • Simard, Christophe1
  • Magaud, Christophe2
  • Adjlane, Racim1
  • Dupas, Quentin1
  • Sallé, Laurent1
  • Manrique, Alain1
  • Bois, Patrick2
  • Faivre, Jean-François2
  • Guinamard, Romain3
  • 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. , (France)
  • 2 Laboratoire Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers, CNRS, Poitiers, France. , (France)
  • 3 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. [email protected] , (France)
Type
Published Article
Journal
Pflügers Archiv - European Journal of Physiology
Publisher
Springer-Verlag
Publication Date
Dec 01, 2020
Volume
472
Issue
12
Pages
1719–1732
Identifiers
DOI: 10.1007/s00424-020-02476-0
PMID: 33047172
Source
Medline
Keywords
Language
English
License
Unknown

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.

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