ALTERATION OF ALPHA-1 NA+,K+-ATPASE RB-86+ INFLUX BY A SINGLE AMINO-ACID SUBSTITUTION

The sodium- and potassium-dependent adenosine triphosphatase (Na +,K+-ATPase) maintains the transmembrane Na+ gradient to which is coupled all active cellular transport systems. The R and S alleles of the gene encoding the Na+,K+-ATPase α1 subunit isoform were identified in Dahl salt-resistant (DR) and Dahl salt-sensitive (DS) rats, respectively. Characterization of the S allele-specific Na+,K+-ATPase α1 complementary DNA identified a leucine substitution of glutamine at position 276. This mutation alters the hydropathy profile of a region in proximity to T3(Na), the trypsin-sensitive site that is only detected in the presence of Na+. This mutation causes a decrease in the rubidium-86 influx of S allele-specific sodium pumps, thus marking a domain in the Na+,K+-ATPase α subunit important for K+ transport, and supporting the hypothesis of a putative role of these pumps in hypertension.