Regulation of T-type Ca v 3.1 channels expression by synthetic glucocorticoid dexamethasone in neonatal cardiac myocytes

The effect of the dexamethasone (Dex) on the regulation of the T-type Ca2+ channel expressions was investigated in primary cultures of neonatal rat ventricular myocytes. We found that Dex (1 μM) increases the T-type Ca2+ current (ICaT) associated with an increase in Cav3.1 mRNA amount. We isolated the upstream region from Cav3.1 encoding gene and tested the activity of the promoter in transfected ventricular myocytes. We found a minimal Dex-responsive region that displayed putative glucocorticoid receptor (GR) and nuclear factor kappa-B (NFκB) targets. The GR selective antagonist, RU38486 (10 μM), nearly turned off the transcriptional activity of Cav3.1 encoding gene, and an NFκB inhibitor, pyrrolodine dithiocarbonate (10 μM), completely abolished the Dex-induced mRNA increase. However, Dex-induced GR and NFκB synthesis and nuclear translocation were not timely related to Cav3.1 mRNA increase. These results indicate that both GR and NFκB were necessary, but not sufficient, to trigger the increase in Cav3.1 mRNA amount. This study showed the relationship between glucocorticoid and T-type channels up-regulation that may be involved in cardiac development and pathology.