Identification of functional corticosteroid response elements involved in regulation of Cacna1g expression in cardiac myocytes

Abstract

We recently reported that corticosteroids increase the expression of the T-type channel Ca(v)3.1 through a transcriptional up-regulation of the Ca(v)3.1 encoding gene cacna1g. The nucleotide sequence analysis of cacna1g promoter revealed putative glucocorticoid response elements (GREs). However, the functional GREs involved in the regulation of cacna1g expression in neonatal cardiac myocytes are unknown. In the present study we have investigated the nuclear targets responsible for the transcriptional regulation of cacna1g. We identified five GREs from the nucleotide sequence of cacna1g promoter. Additionally, using punctual mutagenesis approach, three functional categories of GREs have been identified: (i) GRE-1 involved in promoter activity induced by aldosterone (Aldo, 1 microM); (ii) GRE-4 and GRE-5 involved in promoter activity induced by dexamethasone (Dex, 1 microM); and (iii) GRE-2 and GRE-3 involved in the basal level of neonatal promoter activity. The data presented here lead to better understanding of the molecular mechanisms underlying the regulation of Ca(v)3.1 channel expression by corticosteroids. These new findings have attractive physiological features during cardiac development and pathology such as arrhythmias.