Na,K-ATPase is essential for embryonic heart development in the zebrafish

Shu, X., Cheng, K., Patel, N., Chen, F., Joseph, E., Tsai, H.-J., and Chen, J.-N.
Development (Cambridge, England)   130: 6165-6173 (Journal)
Registered Authors
Chen, Jau-Nian, Joseph, Elaine, Shu, Xiaodong, Tsai, Huai-Jen
heart development, zebrafish, Na,K-ATPase
MeSH Terms
  • Animals
  • Base Sequence
  • DNA Primers
  • Embryo, Nonmammalian/physiology*
  • Gene Expression Regulation, Developmental
  • Genes, Essential
  • Heart/embryology*
  • Heart Defects, Congenital/enzymology
  • Heart Defects, Congenital/genetics
  • In Situ Hybridization
  • Isoenzymes/genetics
  • Isoenzymes/metabolism
  • Molecular Sequence Data
  • Morphogenesis/physiology*
  • Mutation
  • Polymerase Chain Reaction
  • Sodium-Potassium-Exchanging ATPase/genetics*
  • Sodium-Potassium-Exchanging ATPase/metabolism
  • Zebrafish/embryology*
  • Zebrafish Proteins/genetics*
14602677 Full text @ Development
Na,K-ATPase is an essential gene maintaining electrochemical gradients across the plasma membrane. Although previous studies have intensively focused on the role of Na,K-ATPase in regulating cardiac function in the adults, little is known about the requirement for Na,K-ATPase during embryonic heart development. Here, we report the identification of a zebrafish mutant, heart and mind, which exhibits multiple cardiac defects, including the primitive heart tube extension abnormality, aberrant cardiomyocyte differentiation, and reduced heart rate and contractility. Molecular cloning reveals that the heart and mind lesion resides in the alpha1B1 isoform of Na,K-ATPase. Blocking Na,K-ATPase alpha1B1 activity by pharmacological means or by morpholino antisense oligonucleotides phenocopies the patterning and functional defects of heart and mind mutant hearts, suggesting crucial roles for Na,K-ATPase alpha1B1 in embryonic zebrafish hearts. In addition to alpha1B1, the Na,K-ATPase alpha2 isoform is required for embryonic cardiac patterning. Although the alpha1B1 and alpha2 isoforms share high degrees of similarities in their coding sequences, they have distinct roles in patterning zebrafish hearts. The phenotypes of heart and mind mutants can be rescued by supplementing alpha1B1, but not alpha2, mRNA to the mutant embryos, demonstrating that alpha1B1 and alpha2 are not functionally equivalent. Furthermore, instead of interfering with primitive heart tube formation or cardiac chamber differentiation, blocking the translation of Na,K-ATPase alpha2 isoform leads to cardiac laterality defects.
Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes