title: T-type Ca²⁺ channels regulate the exit of cardiac myocytes from the cell cycle after birth.
abstract: T-type Ca(2+) channels (TTCCs) are expressed in the fetal heart and then disappear from ventricular myocytes after birth. The hypothesis examined in this study was the α1G TTCCs' influence in myocyte maturation and their rapid withdrawal from the cell cycle after birth.
  
  
  METHODS
  Cardiac myocytes were isolated from neonatal and adult wild type (WT), α1G-/- and α1G over expressing (α1GDT) mice. Bromodeoxyuridine (BrdU) uptake, myocyte nucleation, cell cycle analysis, and T-type Ca(2+) currents were measured.
  
  
  RESULTS
  All myocytes were mono-nucleated at birth and 35% of WT myocytes expressed functional TTCCs. Very few neonatal myocytes had functional TTCCs in α1G-/- hearts. By the end of the first week after birth no WT or α1G-/- had functional TTCCs. During the first week after birth about 25% of WT myocytes were BrdU+ and became bi-nucleated. Significantly fewer α1G-/- myocytes became bi-nucleated and fewer of these myocytes were BrdU+. Neonatal α1G-/- myocytes were also smaller than WT. Adult WT and α1G-/- hearts were similar in size, but α1G-/- myocytes were smaller and a greater % were mono-nucleated. α1G over expressing hearts were smaller than WT but their myocytes were larger.
  
  
  CONCLUSIONS
  The studies performed show that loss of functional TTCCs is associated with bi-nucleation and myocyte withdrawal from the cell cycle. Loss of α1G TTCCs slowed the transition from mono- to bi-nucleation and resulted in an adult heart with a greater number of small cardiac myocytes. These results suggest that TTCCs are involved in the regulation of myocyte size and the exit of myocytes from the cell cycle during the first week after birth.
authors.affiliation: Cardiovascular Research Center, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.forename: Hajime
authors.initials: H
authors.lastname: Kubo
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Fan
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.forename: Remus
authors.initials: R
authors.lastname: Berretta
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Chen
authors.forename: Thomas
authors.initials: T
authors.lastname: Sharp
authors.forename: Timothy
authors.initials: T
authors.lastname: Starosta
authors.forename: Catherine
authors.initials: C
authors.lastname: Makarewich
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Molkentin
authors.forename: Steven R
authors.initials: SR
authors.lastname: Houser
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D005434:Flow Cytometry; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*
chemical_list: D020747:Calcium Channels, T-Type; D002118:Calcium
keywords: Cardiac myocytes; Cell cycle; T-type Ca(2+) channels