Published online before print August 8, 2008, doi: 10.1161/CIRCRESAHA.108.171835
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on January 10, 2008
Revised on July 29, 2008
Accepted on July 30, 2008
Perinatal Loss of Nkx2-5 Results in Rapid Conduction and Contraction Defects
Laura E. Briggs ;
From the Department of Physiology and Functional Genomics (L.E.B., M.T., A.E.C., M.H.M., A.J.W., T.S., S.P.O., C.S., M.K.R., H.K.), University of Florida College of Medicine, Gainesville; Department of Pediatrics and Developmental Biology (H.W.), Graduate School of Medicine, Tokyo Medical and Dental University, Japan; Cardiology Division (J.T.L.), University of California, San Francisco; Department of Radiation Oncology (N.H.), Washington University School of Medicine, St Louis, Mo; Cardiovascular Research (E.O.W.), Boston University Medical Center, Mass; Department of Bioinformation Analysis (K.Y.), Research Institute of Environmental Medicine, Nagoya University, Aichi, Japan; Department of Molecular Cardiovascular Biology (Y.I.), Yamaguchi University School of Medicine, Ube, Japan; and Cardiovascular Research Center (K.R.C.), Massachusetts General Hospital, Boston.
* To whom correspondence should be addressed. E-mail: hkasahar{at}phys.med.ufl.edu.
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 
-subunit (Nav1.5-), 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.
Key words: conduction • contraction • gene targeting • transcription
This article has been cited by other articles:
 |
|
 |
|
  C. J. Hatcher and C. T. Basson Specification of the Cardiac Conduction System by Transcription Factors Circ. Res., September 25, 2009; 105(7): 620 - 630. [Abstract] [Full Text] [PDF]
|
|