Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects
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 Ca for contraction (conduction-contraction coupling). In addition, expression of ryanodine receptor 2, through which Ca 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. © 2008 American Heart Association, Inc.
Digital Object Identifier (DOI)
Briggs, Laura E.; Takeda, Morihiko; Cuadra, Adolfo E.; Wakimoto, Hiroko; Marks, Melissa H.; Walker, Alexandra J.; Seki, Tsugio; Oh, Suk P.; Lu, Jonathan T.; Sumners, Colin; Raizada, Mohan K.; Horikoshi, Nobuo; Weinberg, Ellen O.; Yasui, Kenji; Ikeda, Yasuhiro; Chien, Kenneth R.; and Kasahara, Hideko, "Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects" (2008). Neurobiology. 694.