| First Author | Briggs LE | Year | 2008 |
| Journal | Circ Res | Volume | 103 |
| Issue | 6 | Pages | 580-90 |
| PubMed ID | 18689573 | Mgi Jnum | J:143802 |
| Mgi Id | MGI:3829107 | Doi | 10.1161/CIRCRESAHA.108.171835 |
| Citation | Briggs LE, et al. (2008) Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects. Circ Res 103(6):580-90 |
| abstractText | 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. |
