Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects
| Autor: | Kenji Yasui, Suk P. Oh, Yasuhiro Ikeda, Melissa H Marks, Tsugio Seki, Alexandra J. Walker, Mohan K. Raizada, Hideko Kasahara, Colin Sumners, Laura E Briggs, Morihiko Takeda, Jonathan T. Lu, Adolfo E. Cuadra, Kenneth R. Chien, Nobuo Horikoshi, Ellen O. Weinberg, Hiroko Wakimoto |
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| Rok vydání: | 2008 |
| Předmět: |
Heart Defects
Congenital medicine.medical_specialty Contraction (grammar) Physiology Action Potentials Mice Transgenic Biology Ryanodine receptor 2 Article Homeobox protein Nkx-2.5 Mice Heart Conduction System Internal medicine medicine Animals Ion channel Homeodomain Proteins Mice Knockout Endoplasmic reticulum Depolarization Myocardial Contraction Long QT Syndrome Endocrinology Animals Newborn Knockout mouse cardiovascular system Homeobox Protein Nkx-2.5 Electrical conduction system of the heart Cardiology and Cardiovascular Medicine Cardiomyopathies Chickens Transcription Factors |
| Zdroj: | Circulation research. 103(6) |
| ISSN: | 1524-4571 |
| Popis: | 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 (Na v 1.5-α), the largest ion channel in the heart responsive for rapid depolarization of the action potential, which leads to increased intracellular Ca 2+ for contraction (conduction–contraction coupling). In addition, expression of ryanodine receptor 2, through which Ca 2+ 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. |
| Databáze: | OpenAIRE |
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