The α2Na+/K+-ATPase is critical for skeletal and heart muscle function in zebrafish.

The Na+/K+-ATPase generates ion gradients across the plasma membrane, essential for multiple cellular functions. In mammals, four different Na+/K+-ATPase a-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+/Cα2+ 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. [ABSTRACT FROM AUTHOR]