The α2Na+/K+-ATPase is critical for skeletal and heart muscle function in zebrafish
The α2Na+/K+-ATPase is critical for skeletal and heart muscle function in zebrafish
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DOI：
10.1242/jcs.115808
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发表时间：
2012-12-15
影响因子：
4
通讯作者：
Lykke-Hartmann, Karin
中科院分区：
文献类型：
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作者：
Doganli, Canan;Kjaer-Sorensen, Kasper;Lykke-Hartmann, Karin
Na+/K+-ATPase在质膜上产生离子梯度，对多种细胞功能至关重要。在哺乳动物中，四种不同的Na+/K+-ATPaseα亚基异构体与特定的细胞类型表达谱和动力学相关。我们发现斑马鱼α-Na-2(+)/K+-ATPase与横纹肌有关，并且击倒导致骨骼肌慢抽动纤维静息膜电位的显著去极化。在α-Na-2(+)/K+-ATPase缺陷胚胎中观察到突然的机械感觉反应，可能与突触后缺陷有关。α-Na-2(+)/K+-ATPase缺乏导致心率减慢，并导致心管左右不对称性消失。敲除Na+/Ca~(2+)交换器的相似表型表明，这两个蛋白在观察到的表型中相互作用。此外，蛋白质组学发现了特定表型相关蛋白的上调和下调，如小白蛋白、CaM、GFAP和多种激酶，从而突出了与α-Na-2(+)/K+-ATPase动态相关的潜在蛋白质组变化。综上所述，我们的发现表明斑马鱼αNa-2(+)/K+-ATPase对骨骼肌和心肌功能是重要的。
The Na+/K+-ATPase generates ion gradients across the plasma membrane, essential for multiple cellular functions. In mammals, four different Na+/K+-ATPase alpha-subunit isoforms are associated with characteristic cell-type expression profiles and kinetics. We found the zebrafish alpha Na-2(+)/K+-ATPase associated with striated muscles and that knockdown causes a significant depolarization of the resting membrane potential in slow-twitch fibers of skeletal muscles. Abrupt mechanosensory responses were observed in alpha Na-2(+)/K+-ATPase-deficient embryos, possibly linked to a postsynaptic defect. The alpha Na-2(+)/K+-ATPase deficiency reduced the heart rate and caused a loss of left-right asymmetry in the heart tube. Similar phenotypes from knockdown of the Na+/Ca2+ exchanger indicated a role for the interplay between these two proteins in the observed phenotypes. Furthermore, proteomics identified up-and downregulation of specific phenotype-related proteins, such as parvalbumin, CaM, GFAP and multiple kinases, thus highlighting a potential proteome change associated with the dynamics of alpha Na-2(+)/K+-ATPase. Taken together, our findings show that zebrafish alpha Na-2(+)/K+-ATPase is important for skeletal and heart muscle functions.