Centre for Membrane Pumps in Cells and Disease-PUMPKIN, Danish National Research Foundation, Aarhus, Denmark.
J Cell Sci. 2012 Dec 15;125(Pt 24):6166-75. doi: 10.1242/jcs.115808. Epub 2012 Oct 24.
The Na(+)/K(+)-ATPase generates ion gradients across the plasma membrane, essential for multiple cellular functions. In mammals, four different Na(+)/K(+)-ATPase α-subunit isoforms are associated with characteristic cell-type expression profiles and kinetics. We found the zebrafish α2Na(+)/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 α2Na(+)/K(+)-ATPase-deficient embryos, possibly linked to a postsynaptic defect. The α2Na(+)/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(+)/Ca(2+) 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 α2Na(+)/K(+)-ATPase. Taken together, our findings show that zebrafish α2Na(+)/K(+)-ATPase is important for skeletal and heart muscle functions.
钠钾泵（Na(+)/K(+)-ATPase）在细胞质膜两侧产生离子梯度，这对多种细胞功能至关重要。在哺乳动物中，有四种不同的 Na(+)/K(+)-ATPaseα 亚基同工型与特征性的细胞类型表达谱和动力学相关。我们发现斑马鱼α2Na(+)/K(+)-ATPase 与横纹肌有关，敲低该蛋白会导致骨骼肌慢肌纤维静息膜电位显著去极化。在α2Na(+)/K(+)-ATPase 缺失的胚胎中观察到突然的机械感觉反应，这可能与突触后缺陷有关。α2Na(+)/K(+)-ATPase 缺乏会降低心率，并导致心脏管腔的左右不对称丧失。Na(+)/Ca(2+)交换蛋白敲低的表型类似，表明这两种蛋白之间的相互作用在观察到的表型中起作用。此外，蛋白质组学鉴定出与特定表型相关的蛋白质（如副甲状腺球蛋白、钙调蛋白、GFAP 和多种激酶）的上调和下调，从而突出了与α2Na(+)/K(+)-ATPase 动力学相关的潜在蛋白质组变化。总之，我们的研究结果表明，斑马鱼α2Na(+)/K(+)-ATPase 对骨骼肌和心肌功能很重要。
