Three differentially expressed Na, K-ATPase α subunit isoforms: Structural and functional implications

We have characterized cDNAs coding for three Na,K-ATPase α subunit isoforms from the rat, a species resistant to ouabain. Northern blot and S1-nuclease mapping analyses revealed that these α subunit mRNAs are expressed in a tissue-specific and developmentally regulated fashion. The mRNA for the α1 isoform, ≃4.5 kb long, is expressed in all fetal and adult rat tissues examined. The α2 mRNA, also ≃4.5 kb long, is expressed predominantly in brain and fetal heart. The α3 cDNA detected two mRNA species: a ≃4.5 kb mRNA present in most tissues and a ≃6 kb mRNA, found only in fetal brain, adult brain, heart, and skeletal muscle. The deduced amino acid sequences of these isoforms are highly conserved. However, significant differences in codon usage and patterns of genomic DNA hybridization indicate that the α subunits are encoded by a multigene family. Structural analysis of the α subunits from rat and other species predicts a polytopic protein with seven membrane-spanning regions. Isoform diversity of the α subunit may provide a biochemical basis for Na,K-ATPase functional diversity.