Disease relevance of Atp1a1

• A putative 1079A-->T mutation in the alpha1 isoform of the Na(+), K(+)-ATPase (Atp1a1) gene of the Dahl salt-sensitive rat inbred by John Rapp (SS/Jr) strain was projected to cause a conformation change in the membrane hydrophobic region of the protein product, possibly resulting in hypertension [1].
• Sodium pump activity in arteries of rats with Goldblatt hypertension [2].
• Sodium pump failure in hypoxia and reoxygenation [3].
• Sodium-pump injury and arrhythmogenic transient depolarizations in catecholamine-induced cardiac hypertrophy [4].

High impact information on Atp1a1

• Sodium pump in skeletal muscle: central nervous system-induced suppression by alpha-adrenoreceptors [5].
• Sodium pump activity and calcium relaxation in vascular smooth muscle of deoxycorticosterone acetate-salt rats [6].
• Sodium pump activity was assessed in vitro in sodium-loaded tail artery and thoracic aorta freshly excised from Dahl salt-sensitive (S) and salt-resistant (R) rats on low (0.4%) or high (8%) NaCl diets for 5 to 7 weeks [7].
• Sodium pump evokes high density pump currents in rat midbrain dopamine neurons [8].
• Sodium pump activity was measured as ouabain-sensitive (86)Rb uptake in freshly dispersed cells containing 20 mM sodium as measured with sodium-binding benzofluran isophthalate [9].

Biological context of Atp1a1

• Our results definitively eliminate the putative A1079T transversion in Atp1a1 as a causative factor underlying hypertension in the GH, spontaneously hypertensive, and SS/Jr rat strains and indicate that alternative candidate genes in the region defined by the chromosome 2 hypertension quantitative trait locus should be examined [1].
• Our previous studies revealed that the promoter region between -77 and +17 of the transcription initiation site of the rat Na,K-ATPase alpha1 subunit gene (Atp1a1) is sufficient for the promoter activity [10].
• Both linkage and use of congenic strains have shown that a chromosome region near the gene for the Na-K-ATPase alpha(1)-subunit (Atp1a1) contained a quantitative trait locus (QTL) for blood pressure (BP) [11].
• We studied Na(+)-K(+) pump activity in erythrocytes of Dahl salt-sensitive (SS/Jr) rats in relation to plasma lipids and blood pressure (BP) and the linkage of polymorphic microsatellite marker D2Arb18 (located within intron 1 and exon 2 of Atp1a1 gene) with various phenotypes in 130 SS/Jr x SR/Jr F(2) rats [12].
• Sodium pump kinetics were unaltered in STZ-DM [13].

Anatomical context of Atp1a1

• Sodium pump activity, not glial spatial buffering, clears potassium after epileptiform activity induced in the dentate gyrus [14].
• Sodium pump activity and contraction of renal artery from spontaneously hypertensive rats [15].
• Sodium pump activity of blood vessels has been reported to decrease in several animal models of hypertension [16].
• Sodium pump activity and norepinephrine responsiveness of femoral arterial smooth muscle from DOCA-salt rats [17].
• Sodium-pump ATPase is known to be a cell membrane enzyme being responsible for vectorial transport of Na+ against electrochemical gradient across the plasma membranes of most cell types [18].

Associations of Atp1a1 with chemical compounds

• In conclusion, abnormal cholesterol metabolism but not the Atp1a1 gene locus might represent an important factor for both high BP and altered Na(+)-K(+) pump function in salt-hypertensive Dahl rats [12].
• Sodium pump inhibition by ouabain (10(-4) M) dramatically enhanced the carbachol depolarizations [19].

Other interactions of Atp1a1

• Atp1a1 mRNA and protein were decreased and Nos2 mRNA and protein were increased in MEM [20].
• The altered expression of those genes in MEM was validated and quantified using real-time polymerase chain reaction and MEM protein expression for Atp1a1, Nos2 and Nfkb1 was studied using Western blot and/or immunohistochemistry assays [20].

References