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 t...

Full description

Saved in:
Bibliographic Details
Published in:Circulation research 2008-09, Vol.103 (6), p.580-590
Main Authors: 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, Kasahara, Hideko
Format: Article
Language:English
Subjects:
Action Potentials - genetics
Animals
Animals, Newborn
Biological and medical sciences
Cardiomyopathies - genetics
Cardiomyopathies - metabolism
Chickens
Fundamental and applied biological sciences. Psychology
Heart Conduction System - growth & development
Heart Conduction System - physiology
Heart Defects, Congenital - genetics
Heart Defects, Congenital - metabolism
Homeobox Protein Nkx-2.5
Homeodomain Proteins - genetics
Long QT Syndrome - genetics
Long QT Syndrome - metabolism
Mice
Mice, Knockout
Mice, Transgenic
Myocardial Contraction - genetics
Transcription Factors - deficiency
Transcription Factors - genetics
Vertebrates: cardiovascular system
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0009-7330
1524-4571
DOI:10.1161/CIRCRESAHA.108.171835