Ventricular hypertrophy induced by mineralocorticoid treatment or aortic stenosis differentially regulates the expression of cardiac K+ channels in the rat.

Abstract

Rats treated with DOCA salts and subjected to abdominal aortic stenosis display left ventricle hypertrophy associated with a decrease in cardiac I(to) current density and prolongation of the action potential duration. We investigated the molecular basis of these electrophysiological defects by analyzing the amount of mRNA corresponding to the genes encoding the a subunits of the left ventricle K+ channel at the steady state. The mRNAs corresponding to the a subunits of the K+ channel (Kv1.2, Kv1.4, Kv1.5, Kv2. 1, Kv4.2 and Kv4.3) were measured by quantitative RT-PCR using a specific Kv internal standard. In control rats, the Kvl.5 gene was only expressed at a low level, whereas the Kv4.2 and Kv4.3 genes were expressed at a high level. Regardless of the etiology of the hypertrophy, the amounts of Kv1.4 and Kv1.5 mRNAwere similar in treated, sham and control rats. The amounts of Kv1.2 and Kv2.1 mRNA were markedly lower in DOCA-salt treated rats (66%) than in sham-DOCA rats, but no effect was observed after stenosis. The very conservative Kv4.2 and Kv4.3 genes were found to be downregulated simultaneously in both type of hypertrophy. However, the steady-state amount of Kv4 mRNA was even lower in rats with DOCA-salt-induced hypertrophy than in those with stenosis-induced ventricular hypertrophy. Therefore, the decrease in I(to) density, consecutively to pressure- and volume-overload, is due to a large decrease in the amount of Kv4.2 and Kv4.3 mRNA. In addition, DOCA-salt treatment alters the amounts of Kv transcripts independently to cardiac hypertrophy, suggesting that the mineralocorticoid may be involved in Kv gene expression.

• Authors: Veronique Capuano, Yann Ruchon, Sylvestre Antoine, Marie-Claire Sant, Jean-François Renaud
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 237 Issue 1-2 Pg. 1-10 (Aug 2002) ISSN: 0300-8177 [Print] Netherlands
• PMID: 12236575 (Publication Type: Journal Article)

Chemical References

• Mineralocorticoids
• Potassium Channels
• RNA, Messenger
• Desoxycorticosterone
• DNA
• Cyclophilin A

Topics

• Animals
• Aortic Valve Stenosis (complications)
• Cardiomegaly (chemically induced, pathology)
• Cyclophilin A (metabolism)
• DNA (metabolism)
• Desoxycorticosterone (pharmacology)
• Down-Regulation
• Gene Expression Regulation
• Hypertrophy
• Male
• Mineralocorticoids (pharmacology)
• Myocardium (pathology)
• Potassium Channels (biosynthesis)
• RNA, Messenger (metabolism)
• Rats
• Rats, Wistar
• Reverse Transcriptase Polymerase Chain Reaction