title: The α2Na+/K+-ATPase is critical for skeletal and heart muscle function in zebrafish.
abstract: 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.
authors.affiliation: Centre for Membrane Pumps in Cells and Disease-PUMPKIN, Danish National Research Foundation, Aarhus, Denmark.
authors.forename: Canan
authors.initials: C
authors.lastname: Doganli
authors.forename: Kasper
authors.initials: K
authors.lastname: Kjaer-Sorensen
authors.forename: Christopher
authors.initials: C
authors.lastname: Knoeckel
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Beck
authors.forename: Jens Randel
authors.initials: JR
authors.lastname: Nyengaard
authors.forename: Bent
authors.initials: B
authors.lastname: Honoré
authors.forename: Poul
authors.initials: P
authors.lastname: Nissen
authors.forename: Angeles
authors.initials: A
authors.lastname: Ribera
authors.forename: Claus
authors.initials: C
authors.lastname: Oxvig
authors.forename: Karin
authors.initials: K
authors.lastname: Lykke-Hartmann
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D005260:Female; D055785:Gene Knockdown Techniques; D008297:Male; D008564:Membrane Potentials; D018482:Muscle, Skeletal / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D000254:Sodium-Potassium-Exchanging ATPase