| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Pharmacology and toxicology, University of Lausanne, Lausanne, Switzerland
2 Pharmacology and toxicology, University of Lausanne, Lausanne, Switzerland; Cardiology, CHUV, Lausanne, Switzerland
* To whom correspondence should be addressed. E-mail: hugues.abriel{at}unil.ch.
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. Ten nM aldosterone increased the INa by 23%. In 24 h-coincubation experiments, using 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, whilst RU38486 (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 up-regulates the cardiac INa and suggest that this phenomenon may contribute to the HF-induced electrical remodeling process that may be reversed by spironolactone.
This article has been cited by other articles:
|
|
 |
|
  G. Michael, L. Xiao, X.-Y. Qi, D. Dobrev, and S. Nattel Remodelling of cardiac repolarization: how homeostatic responses can lead to arrhythmogenesis Cardiovasc Res, October 22, 2008; (2008) cvn266v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Pitt, A. Ahmed, T. E. Love, H. Krum, J. Nicolau, J. S. Cardoso, A. Parkhomenko, M. Aschermann, R. Corbalan, H. Solomon, et al. History of Hypertension and Eplerenone in Patients With Acute Myocardial Infarction Complicated by Heart Failure Hypertension, August 1, 2008; 52(2): 271 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Muto, N. Ueda, T. Opthof, T. Ohkusa, K. Nagata, S. Suzuki, Y. Tsuji, M. Horiba, J.-K. Lee, H. Honjo, et al. Aldosterone modulates If current through gene expression in cultured neonatal rat ventricular myocytes Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2710 - H2718. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Pitt and G. S. Pitt Added Benefit of Mineralocorticoid Receptor Blockade in the Primary Prevention of Sudden Cardiac Death Circulation, June 12, 2007; 115(23): 2976 - 2982. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Gavillet, J.-S. Rougier, A. A. Domenighetti, R. Behar, C. Boixel, P. Ruchat, H.-A. Lehr, T. Pedrazzini, and H. Abriel Cardiac Sodium Channel Nav1.5 Is Regulated by a Multiprotein Complex Composed of Syntrophins and Dystrophin Circ. Res., August 18, 2006; 99(4): 407 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Pitt and B. Pitt Aldosterone, ion channels, and sudden death: another piece of the circle? Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2176 - H2177. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
