| First Author | Koushik SV | Year | 2001 |
| Journal | FASEB J | Volume | 15 |
| Issue | 7 | Pages | 1209-11 |
| PubMed ID | 11344090 | Mgi Jnum | J:69362 |
| Mgi Id | MGI:1934493 | Doi | 10.1096/fj.00-0696fje |
| Citation | Koushik SV, et al. (2001) Targeted inactivation of the sodium-calcium exchanger (Ncx1) results in the lack of a heartbeat and abnormal myofibrillar organization. FASEB J 15(7):1209-11 |
| abstractText | Contraction of cardiac muscle is triggered by an intracellular buildup of Ca2+ during excitationcontraction (E-C) coupling. The Na+/Ca2+ exchanger (Ncx1) is highly expressed in cardiomyocytes and is thought to serve a housekeeping function by maintaining a low intracellular Ca2+ concentration. However, its role in E-C coupling is controversial. To determine the precise role of Na+/Ca2+ exchange in development of the mammalian heart, we used gene targeting to delete Ncx1. Heterozygous mice are normal and fertile, whereas Ncx1-null embryos are growth-retarded and survive to 11.0 days postcoitum but lack a spontaneously beating heart. Moreover, normal heart morphogenesis (specification, looping, and chamber formation) occurred relatively normally within Ncx1-null embryos. In addition, Ncx1-nulls displayed relatively normal transient Ca2+ signals when electrically stimulated. This suggests that the Ca2+ delivery mechanism was fundamentally intact, and that Ncx1-null cardiomyocytes can regulate intracellular Ca2+ concentrations despite the absence of Ncx1. However, ultrastructural analysis revealed that Ncx1-null cardiomyocytes have a complete lack of organized myofibrils and Zlines when compared with normal littermates. These data demonstrate that Ncx-1 is a Ca2+- handling gene that is essential for normal cardiomyocyte development and function and may serve as an animal model for functionally related human congenital heart defects. |
