Title

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

Document Type

Article

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 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.

Publication Date

9-12-2008

Publication Title

Circulation Research

ISSN

00097330

E-ISSN

15244571

Volume

103

Issue

6

First Page

580

Last Page

590

PubMed ID

18689573

Digital Object Identifier (DOI)

10.1161/CIRCRESAHA.108.171835

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