The alpha2Na+/K+-ATPase is critical for skeletal and heart muscle function in zebrafish
- Authors
- Doganli, C., Kjaer-Sorensen, K., Knoeckel, C., Beck, H.C., Nyengaard, J.R., Honoré, B., Nissen, P., Ribera, A., Oxvig, C., and Lykke-Hartmann, K.
- ID
- ZDB-PUB-121102-40
- Date
- 2012
- Source
- Journal of Cell Science 125(24): 6166-6175 (Journal)
- Registered Authors
- Doganli, Canan
- Keywords
- Na+/K+-ATPase α2-isoform, Familial hemiplegic migraine type 2 (FHM2), Skeletal and heart muscle function, Resting membrane potential, Mechanosensory response, Proteomics
- MeSH Terms
-
- Animals
- Cell Membrane/enzymology
- Female
- Gene Knockdown Techniques
- Male
- Membrane Potentials
- Muscle, Skeletal/enzymology*
- Myocardium/enzymology*
- Sodium-Potassium-Exchanging ATPase/deficiency
- Sodium-Potassium-Exchanging ATPase/genetics
- Sodium-Potassium-Exchanging ATPase/metabolism*
- Zebrafish
- PubMed
- 23097043 Full text @ J. Cell Sci.
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 α2Na+/K+-ATPase 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 observed by knockdown of the Na+/Ca2+ exchanger indicated a role for the interplay between these two proteins on the observed phenotypes. Furthermore, proteomics identified up- and down-regulation 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 display that zebrafish α2Na+/K+-ATPase is important for skeletal and heart muscle functions.