Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects

LE Briggs, M Takeda, AE Cuadra, H Wakimoto… - Circulation …, 2008 - Am Heart Assoc
LE Briggs, M Takeda, AE Cuadra, H Wakimoto, MH Marks, AJ Walker, T Seki, SP Oh, JT Lu…
Circulation research, 2008Am Heart Assoc
Homeobox transcription factor Nkx2-5, highly expressed in heart, is a critical factor during
early embryonic cardiac development. In this study, using tamoxifen-inducible Nkx2-5
knockout mice, we demonstrate the role of Nkx2-5 in conduction and contraction in neonates
within 4 days after perinatal tamoxifen injection. Conduction defect was accompanied by
reduction in ventricular expression of the cardiac voltage-gated Na+ channel pore-forming α-
subunit (Nav1. 5-α), the largest ion channel in the heart responsive for rapid depolarization …
Homeobox transcription factor Nkx2-5, highly expressed in heart, is a critical factor during early embryonic cardiac development. In this study, using tamoxifen-inducible Nkx2-5 knockout mice, we demonstrate the role of Nkx2-5 in conduction and contraction in neonates within 4 days after perinatal tamoxifen injection. Conduction defect was accompanied by reduction in ventricular expression of the cardiac voltage-gated Na+ channel pore-forming α-subunit (Nav1.5-α), the largest ion channel in the heart responsive for rapid depolarization of the action potential, which leads to increased intracellular Ca2+ for contraction (conduction–contraction coupling). In addition, expression of ryanodine receptor 2, through which Ca2+ is released from sarcoplasmic reticulum, was substantially reduced in Nkx2-5 knockout mice. These results indicate that Nkx2-5 function is critical not only during cardiac development but also in perinatal hearts, by regulating expression of several important gene products involved in conduction and contraction.
Am Heart Assoc