Rat cardiac ventricle has two Na+,K+-ATPases with different affinities for ouabain: developmental changes in immunologically different catalytic subunits.
The mechanism of the inotropic effect of cardiac glycosides on the heart has long been controversial. Inotropic effects at low concentrations of cardiac glycosides indicate more than one class of receptor or more than one cellular mechanism. In the brain of the rat, high- and low-affinity cardiac glycoside receptors have been shown to be associated with two structurally different isoforms of the catalytic subunit of the Na+,K+-ATPase, termed alpha and alpha(+). Evidence is presented here that the high- and low-affinity sites in rat cardiac ventricle are associated with Na+,K+-ATPase catalytic subunit forms similar to the alpha(+) and alpha forms in the brain. Membranes from the rat ventricle contained polypeptides with the electrophoretic mobilities of alpha and alpha(+), which could be stained by isoform-specific anti-Na+,K+-ATPase antibodies on electrophoretic blots. Both polypeptides also displayed Na+-stimulated phosphorylation with [gamma-32P]ATP. Inhibition of Na+,K+-ATPase activity by ouabain demonstrated the presence of both high- and low-affinity ATPases proportional to the presence of the alpha(+) and alpha polypeptides. The ratios of the two isoforms changed with postnatal maturation, paralleling known changes in cardiac physiology and cardiac glycoside sensitivity. Cardiac glycoside sensitivity can evidently be regulated at the level of gene expression by developmental signals.
Sweadner
K J
KJ
Harvard Medical School, Boston, MA.
Farshi
S K
SK
D000367:Age Factors; D000818:Animals; D001665:Binding Sites; D006321:Heart / Q000254:growth & development*; D007163:Immunosorbent Techniques; D007527:Isoenzymes / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology*; D010042:Ouabain / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000276:immunology / Q000378:metabolism*
D007527:Isoenzymes; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase