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1Department of Pharmacology and Toxicology, University of Lausanne, Switzerland; and 2Service of Cardiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
The role of aldosterone in the pathogenesis of heart failure (HF) is still poorly understood. Recently, aldosterone has been shown to modulate the function of cardiac Ca2+ and K+ channels, thus playing a role in the electrical remodeling process. The goal of this work was to investigate the role of aldosterone on the cardiac Na+ current (INa). We analyzed the effects of aldosterone on INa in isolated adult mouse ventricular myocytes, using the whole cell patch-clamp technique. After 24 h incubation with 1 µM aldosterone, the INa density was significantly increased (+55%), without alteration of the biophysical properties and the cell membrane capacitance. Aldosterone (10 nM) increased the INa by 23%. In 24-h coincubation experiments, with the use of actinomycin D, cycloheximide, or brefeldin A, the effect of aldosterone on INa was abolished. Spironolactone (mineralocorticoid receptor antagonist, 10 µM) prevented the 1 µM aldosterone-dependent INa increase, whereas RU-38486 (glucocorticoid receptor antagonist, 10 µM) did not. The action potential duration (APD) was longer in aldosterone-treated (APD90: +53%) than in control myocytes. In addition, the L-type Ca2+ current was also upregulated (+48%). We performed quantitative RT-PCR measurements and Western blots to quantify the mRNA and protein levels of Nav1.5 and Cav1.2 (main channels mediating cardiac INa and ICa), but no significant difference was found. In conclusion, this study shows that aldosterone upregulates the cardiac INa and suggest that this phenomenon may contribute to the HF-induced electrical remodeling process that may be reversed by spironolactone.
sodium channels; calcium channels; electrophysiology; spironolactone
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