Copyright © 2005, European Society of Cardiology
Aldosterone increases T-type calcium channel expression and in vitro beating frequency in neonatal rat cardiomyocytes
aDivision of Endocrinology and Diabetology, Department of Internal Medicine, University Hospital, CH-1211 Geneva 14, Switzerland
bLaboratory of Clinical Chemistry, Department of Clinical Pathology, University Hospital, CH-1211 Geneva 14, Switzerland
cINSERM U-637, Lab. Cardiovascular Physiopathology, CHU Arnaud de Villeneuve, Montpellier, France
dIGF, CNRS UMR 5203, IGH, Montpellier, France
* Corresponding author. Division of Endocrinology and Diabetology, University Hospital, 24 rue Micheli-du-Crest, CH-1211 Geneva 14, Switzerland. Tel.: +41 22 3729320; fax: +41 22 3729329. Email address: michel.rossier{at}hcuge.ch
Objective: Although aldosterone has been implicated in the pathogenesis of cardiac hypertrophy and heart failure, its cellular mechanism of action on cardiomyocyte function is not yet completely elucidated. This study was designed to investigate the effect of aldosterone on calcium channel expression and cardiomyocyte contraction frequency.
Methods: Cultured neonatal rat ventricular cardiomyocytes were stimulated in vitro with 1 µmol/L aldosterone for 24 h. Calcium currents were then measured with the patch clamp technique, while calcium channel expression was assessed by real-time RT-PCR.
Results: In the present study, we show that aldosterone increases Ca2+ currents by inducing channel expression. Indeed, aldosterone led to a substantial increase of L- and T-type Ca2+ current amplitudes, and we found a concomitant 55% increase of the mRNA coding for 
1C and β2 subunits of cardiac L channels. Although T-type currents were relatively small under control conditions, they increased 4-fold and T channel 1H isoform expression rose in the same proportion after aldosterone treatment. Because T channels have been implicated in the modulation of membrane electrical activity, we investigated whether aldosterone affects the beating frequency of isolated cardiomyocytes. In fact, aldosterone dose-dependently increased the spontaneous beating frequency more than 4-fold. This effect of aldosterone was prevented by actinomycin D and spironolactone and reduced by RU486, suggesting a mixed mineralocorticoid/glucocorticoid receptor-dependent transcriptional mechanism. Moreover, inhibition of T currents with Ni2+ or mibefradil significantly reduced beating frequency towards control values, while conditions affecting L-type currents completely blocked contractions.
Conclusion: Aldosterone modulates the expression of cardiac voltage-operated Ca2+ channels and accelerates beating in cultured neonatal rat ventricular myocytes. This chronotropic action of aldosterone appears to be linked to increased T channel activity and could contribute to the deleterious effect of an excess of this steroid in vivo on cardiac function.
KEYWORDS Renin angiotensin system; Ca-channel; Gene expression; Contractile function; Ventricular arrhythmias
Time for primary review 18 days
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