Functional and molecular characterization of a T-type Ca2+ channel during fetal and postnatal rat heart development

L. FERRON, V. CAPUANO, E. DEROUBAIX, A. COULOMBE AND J.-F. RENAUD. Functional and Molecular Characterization of a T-type Ca2+ Channel During Fetal and Postnatal Rat Heart Development. Journal of Molecular and Cellular Cardiology (2002) 34, 533-546. T type calcium current (I-CaT) is distributed among a large variety of species and tissues. The main functions of I-CaT are thought to be related to pacemaker activity and to the cell cycle. Using the whole-cell patch-clamp configuration, we showed that fetal rat ventricular cells exhibit an I-CaT with electrophysiological and pharmacological characteristics similar to those already described for this current. We investigated I-CaT density and found that this current was mainly expressed in fetal cells and remained stable until birth (3.1 +/- 0.3 pA/pF for 18-day-old fetus, n=9). I-CaT density decreased soon after birth (2.0 +/- 0.3 pA/pF, n=6, 1.1 +/- 0.2 pA/pF, n=5, for 1- and 5-day-old rats, respectively) and was no longer detected in 21-day-old rats. The rat ventricular cells express an alpha1H isoform in addition to a homologous alpha1G variant. Interestingly, the Ni2+ sensitivity of I-CaT indicates that in newborn myocytes, I-CaT is only generated by alpha1G subunits, whereas both alpha1G and alpha1H subunits participate in the fetal I-CaT. Moreover, the relative contribution of each subunit varies during fetal developmental stages, with a major contribution of alpha1H in 16-day-old fetuses. Through quantitative RT-PCR we showed that the amount of both alpha1G and alpha1H transcripts are developmentally regulated. In fetuses of less than 18 days and in newborn rats after 1 day old, the transcriptional levels of alpha1G and alpha1H subunits clearly mismatch the functional contribution of these subunits to I-CaT. However, in perinatal period, the amount of alpha1G mRNA seems to be in accordance to alpha1G-related I-CaT density. In conclusion, we showed that I-CaT is mainly expressed during fetal stages, that alpha1G and alpha1H differentially participate to I-CaT and that alpha1G and alpha1H isoforms are regulated by both transcriptional and post-transcriptional mechanisms. (C) 2002 Elsevier Science Ltd. All rights reserved.