Pathophysiological Significance of T-type Ca²⁺ Channels:
Expression of T-type Ca²⁺ Channels in Fetal and Diseased Heart

Abstract

Re-expression of fetal genes has been considered to underlie ionic remodeling in diseased heart. T-type Ca²⁺ channels have been reported to be functionally expressed in embryonic hearts. In this review, we summarize developmental changes of T-type Ca²⁺ channels in mouse ventricles from 9.5 days postcoitum (dpc) to adulthood, using patch clamp and quantitative PCR. In addition, we introduced T-type Ca²⁺ channel expression in hypertrophied ventricles caused by myocardial infarction (MI) and aortic banding (AOB). Substantial T-type Ca²⁺ channel current was recorded at both 9.5 and 18 dpc. The currents were inhibited by Ni²⁺ at low concentrations. The current was not detectable in the adult stage. Ca_v3.2 (α_1H) mRNA is expressed dominantly at both 9.5 and 18 dpc. Ca_v3.1 (α_1G) increases from 9.5 to 18 dpc, but remains at low level compared with Ca_v3.2. In contrast, Ca_v3.1 is greater than Ca_v3.2 at the adult stage. In MI, Ca_v3.1 mRNA correlates negatively with brain natriuretic peptide (BNP) mRNA, whereas Ca_v3.2 mRNA correlates positively with BNP mRNA. In AOB, these correlations are weak. We also analyzed the neuron-restrictive silencer factor (NRSF) in these hearts because it is the suppressor of transcription of the fetal cardiac gene program. The negative correlation between NRSF and BNP was stronger in MI than in AOB. Our findings show that Ca_v3.2 underlies the functional T-type Ca²⁺ channel in embryonic heart and suggest that NRSF may regulate Ca_v3.2 expression in diseased hearts.