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 ?1G TTCCs' influence in myocyte maturation and their rapid withdrawal from the cell cycle after birth.Cardiac myocytes were isolated from neonatal and adult wild type (WT), ?1G-/- and ?1G over expressing (?1GDT) mice. Bromodeoxyuridine (BrdU) uptake, myocyte nucleation, cell cycle analysis, and T-type Ca(2+) currents were measured.All myocytes were mono-nucleated at birth and 35% of WT myocytes expressed functional TTCCs. Very few neonatal myocytes had functional TTCCs in ?1G-/- hearts. By the end of the first week after birth no WT or ?1G-/- had functional TTCCs. During the first week after birth about 25% of WT myocytes were BrdU+ and became bi-nucleated. Significantly fewer ?1G-/- myocytes became bi-nucleated and fewer of these myocytes were BrdU+. Neonatal ?1G-/- myocytes were also smaller than WT. Adult WT and ?1G-/- hearts were similar in size, but ?1G-/- myocytes were smaller and a greater % were mono-nucleated. ?1G over expressing hearts were smaller than WT but their myocytes were larger.The studies performed show that loss of functional TTCCs is associated with bi-nucleation and myocyte withdrawal from the cell cycle. Loss of ?1G 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.

SUBMITTER: Wang F 

PROVIDER: S-EPMC3888788 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature