title: Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects.
abstract: 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 alpha-subunit (Na(v)1.5-alpha), 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.
authors.affiliation: University of Florida College of Medicine, 1600 SW Archer Rd, M-540, Gainesville, FL 32610-0274, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Briggs
authors.forename: Morihiko
authors.initials: M
authors.lastname: Takeda
authors.forename: Adolfo E
authors.initials: AE
authors.lastname: Cuadra
authors.forename: Hiroko
authors.initials: H
authors.lastname: Wakimoto
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Marks
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Walker
authors.forename: Tsugio
authors.initials: T
authors.lastname: Seki
authors.forename: Suk P
authors.initials: SP
authors.lastname: Oh
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Lu
authors.forename: Colin
authors.initials: C
authors.lastname: Sumners
authors.forename: Mohan K
authors.initials: MK
authors.lastname: Raizada
authors.forename: Nobuo
authors.initials: N
authors.lastname: Horikoshi
authors.forename: Ellen O
authors.initials: EO
authors.lastname: Weinberg
authors.forename: Kenji
authors.initials: K
authors.lastname: Yasui
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Chien
authors.forename: Hideko
authors.initials: H
authors.lastname: Kasahara
mesh_terms: D000200:Action Potentials / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism; D002645:Chickens; D006329:Heart Conduction System / Q000254:growth & development* / Q000502:physiology; D006330:Heart Defects, Congenital / Q000235:genetics / Q000378:metabolism; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000235:genetics*; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors