T-type Ca2+ channels regulate the exit of cardiac myocytes from the cell cycle after birth

T-type Ca2+ channels (TTCCs) are expressed in the fetal heart and then disappear from ventricular myocytes after birth. The hypothesis examined in this study was the alpha 1G 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), alpha 1G-/- and alpha 1G over expressing (alpha 1GDT) mice. Bromodeoxyuridine (BrdU) uptake, myocyte nucleation, cell cycle analysis, and T-type Ca2+ 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 alpha 1G-/- hearts. By the end of the first week after birth no WT or alpha 1G-/- had functional TTCCs. During the first week after birth about 25% of WT myocytes were BrdU+ and became bi-nucleated. Significantly fewer alpha 1G-/- myocytes became bi-nucleated and fewer of these myocytes were BrdU+. Neonatal alpha 1G-/- myocytes were also smaller than WT. Adult WT and alpha 1G-/- hearts were similar in size, but alpha 1G-/- myocytes were smaller and a greater % were mono-nucleated. alpha 1G 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 alpha 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. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.