Na,K-ATPase is essential for embryonic heart development in the zebrafish
Na,K-ATPase is essential for embryonic heart development in the zebrafish
复制标题
DOI：
10.1242/dev.00844
复制
发表时间：
2003-12-01
期刊：
影响因子：
4.6
通讯作者：
Chen, JN
中科院分区：
文献类型：
--
作者：
Shu, XD;Cheng, KR;Chen, JN
Na，K-ATP酶是维持跨膜电化学梯度的重要基因。虽然以往的研究集中在Na，K-ATP酶在成人心脏功能调节中的作用，但对胚胎心脏发育对Na，K-ATP酶的需求知之甚少。在这里，我们报告的斑马鱼突变，心脏和心灵，表现出多种心脏缺陷，包括原始心管延伸异常，异常心肌细胞分化，降低心率和收缩力的鉴定。分子克隆显示，心脏和精神病变位于Na，K-ATP酶的α 1B 1亚型。通过药理学手段或通过吗啉代反义寡核苷酸阻断Na，K-ATP酶α 1B 1活性表型模拟心脏和精神突变心脏的模式和功能缺陷，表明Na，K-ATP酶α 1B 1在胚胎斑马鱼心脏中的关键作用。除了alpha 1B 1，Na，K-ATP酶alpha 2亚型是胚胎心脏模式所必需的。虽然alpha 1B 1和alpha 2亚型在其编码序列中具有高度的相似性，但它们在斑马鱼心脏的模式中具有不同的作用。心脏和精神突变的表型可以通过向突变胚胎补充α 1B 1而不是α 2 mRNA来挽救，这表明α 1B 1和α 2在功能上并不等同。此外，阻断Na，K-ATP酶α 2亚型的翻译导致心脏偏侧性缺陷，而不是干扰原始心管形成或心腔分化。
Na,K-ATPase is an essential gene maintaining electrochemical gradients across the plasma membrane. Although previous studies have intensively focused on the role of Na,K-ATPase in regulating cardiac function in the adults, little is known about the requirement for Na,K-ATPase during embryonic heart development. Here, we report the identification of a zebrafish mutant, heart and mind, which exhibits multiple cardiac defects, including the primitive heart tube extension abnormality, aberrant cardiomyocyte differentiation, and reduced heart rate and contractility. Molecular cloning reveals that the heart and mind lesion resides in the alpha1B1 isoform of Na,K-ATPase. Blocking Na,K-ATPase alpha1B1 activity by pharmacological means or by morpholino antisense oligonucleotides phenocopies the patterning and functional defects of heart and mind mutant hearts, suggesting crucial roles for Na,K-ATPase alpha1B1 in embryonic zebrafish hearts. In addition to alpha1B1, the Na,K-ATPase alpha2 isoform is required for embryonic cardiac patterning. Although the alpha1B1 and alpha2 isoforms share high degrees of similarities in their coding sequences, they have distinct roles in patterning zebrafish hearts. The phenotypes of heart and mind mutants can be rescued by supplementing alpha1B1, but not alpha2, mRNA to the mutant embryos, demonstrating that alpha1B1 and alpha2 are not functionally equivalent. Furthermore, instead of interfering with primitive heart tube formation or cardiac chamber differentiation, blocking the translation of Na,K-ATPase alpha2 isoform leads to cardiac laterality defects.