Circulation research · 2008
Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects.
Сравнительное исследованиеСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Briggs Laura E, Takeda Morihiko, Cuadra Adolfo E, Wakimoto Hiroko, Marks Melissa H, Walker Alexandra J, Seki Tsugio, Oh Suk P, Lu Jonathan T, Sumners Colin, Raizada Mohan K, Horikoshi Nobuo, Weinberg Ellen O, Yasui Kenji, Ikeda Yasuhiro, Chien Kenneth R, Kasahara Hideko
Аннотация
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.