title: Subtype switching of T-type Ca 2+ channels from Cav3.2 to Cav3.1 during differentiation of embryonic stem cells to cardiac cell lineage.
abstract: BACKGROUND
  The developmental changes of Ni(2+)-sensitivity to automaticity of Nkx2.5-positive cells derived from mouse embryonic stem cell have been identified, suggesting developmental regulation of expressing Ni(2+)-sensitive T-type Ca(2+) channel, although the mechanism of the change has not been fully studied.
  
  
  RESULTS
  Transcripts of Cav3.2, Cav3.1 and Cav1.2 genes of beating Nkx2.5-positive cells, which encode the Ni(2+)-sensitive T-type Ca(2+) channel, Ni(2+)-insensitive T-type Ca(2+) channel, and L-type Ca(2+) channel, respectively, were investigated by real-time reverse-transcriptase-polymerase chain reaction, and the current density of each channel was measured by patch-clamp techniques at the early and late stages of differentiation. The expression of the Cav3.2 transcript predominated in the early stage whereas those of Cav3.1 and Cav1.2 transcripts were upregulated in the late stage, which was consistent with the change in each current density, suggesting the expression of channel proteins is largely determined at the transcriptional level.
  
  
  CONCLUSIONS
  The results indicate that the mechanism of change of Ni(2+)-sensitivity is partly, if not completely, the subtype switch of T-type Ca(2+) channel from Cav3.2 to Cav3.1 at the transcriptional level, and that the expression of the L-type Ca(2+) channel might have an attenuating effect on Ni(2+)-sensitivity to automaticity in the late stage of differentiation.
authors.affiliation: Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science, Japan.
authors.forename: Einosuke
authors.initials: E
authors.lastname: Mizuta
authors.forename: Junichiro
authors.initials: J
authors.lastname: Miake
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yano
authors.forename: Hitomi
authors.initials: H
authors.lastname: Furuichi
authors.forename: Kasumi
authors.initials: K
authors.lastname: Manabe
authors.forename: Norihito
authors.initials: N
authors.lastname: Sasaki
authors.forename: Osamu
authors.initials: O
authors.lastname: Igawa
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Hoshikawa
authors.forename: Chiaki
authors.initials: C
authors.lastname: Shigemasa
authors.forename: Eiji
authors.initials: E
authors.lastname: Nanba
authors.forename: Haruaki
authors.initials: H
authors.lastname: Ninomiya
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hidaka
authors.forename: Takayuki
authors.initials: T
authors.lastname: Morisaki
authors.forename: Fumihito
authors.initials: F
authors.lastname: Tajima
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hisatome
mesh_terms: D000818:Animals; D020747:Calcium Channels, T-Type / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
chemical_list: C498197:Cacna1g protein, mouse; C504883:Cacna1h protein, mouse; D020747:Calcium Channels, T-Type