title: 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 Ca(2+) channels have been reported to be functionally expressed in embryonic hearts. In this review, we summarize developmental changes of T-type Ca(2+) channels in mouse ventricles from 9.5 days postcoitum (dpc) to adulthood, using patch clamp and quantitative PCR. In addition, we introduced T-type Ca(2+) channel expression in hypertrophied ventricles caused by myocardial infarction (MI) and aortic banding (AOB). Substantial T-type Ca(2+) channel current was recorded at both 9.5 and 18 dpc. The currents were inhibited by Ni(2+) at low concentrations. The current was not detectable in the adult stage. Ca(v)3.2 (alpha(1H)) mRNA is expressed dominantly at both 9.5 and 18 dpc. Ca(v)3.1 (alpha(1G)) increases from 9.5 to 18 dpc, but remains at low level compared with Ca(v)3.2. In contrast, Ca(v)3.1 is greater than Ca(v)3.2 at the adult stage. In MI, Ca(v)3.1 mRNA correlates negatively with brain natriuretic peptide (BNP) mRNA, whereas Ca(v)3.2 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(v)3.2 underlies the functional T-type Ca(2+) channel in embryonic heart and suggest that NRSF may regulate Ca(v)3.2 expression in diseased hearts.
authors.affiliation: Department of Bioinformation Analysis, Research Institute of Environmental Medicine, Nagoya University, Japan. kenji@riem.nagoya-u.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Yasui
authors.forename: Noriko
authors.initials: N
authors.lastname: Niwa
authors.forename: Haruki
authors.initials: H
authors.lastname: Takemura
authors.forename: Tobias
authors.initials: T
authors.lastname: Opthof
authors.forename: Takao
authors.initials: T
authors.lastname: Muto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Horiba
authors.forename: Atsuya
authors.initials: A
authors.lastname: Shimizu
authors.forename: Jong-Kook
authors.initials: JK
authors.lastname: Lee
authors.forename: Haruo
authors.initials: H
authors.lastname: Honjo
authors.forename: Kaichiro
authors.initials: K
authors.lastname: Kamiya
authors.forename: Itsuo
authors.initials: I
authors.lastname: Kodama
mesh_terms: D000818:Animals; D020747:Calcium Channels, T-Type / Q000032:analysis / Q000502:physiology*; D005318:Fetal Heart / Q000378:metabolism*; D006801:Humans; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*
chemical_list: D020747:Calcium Channels, T-Type