Isoform specificity of cardiac glycosides binding to human Na+,K+-ATPase α1β1, α2β1 and α3β1

Abstract Cardiac glycosides inhibit the Na + ,K + -ATPase and are used for the treatment of symptomatic heart failure and atrial fibrillation. In human heart three isoforms of Na + ,K + -ATPase are expressed: α 1 β 1 , α 2 β 1 and α 3 β 1 . It is unknown, if clinically used cardiac glycosides differ in isoform specific affinities, and if the isoforms have specific subcellular localization in human cardiac myocytes. Human Na + ,K + -ATPase isoforms α 1 β 1 , α 2 β 1 and α 3 β 1 were expressed in yeast which has no endogenous Na + ,K + -ATPase. Isoform specific affinities of digoxin, digitoxin, β-acetyldigoxin, methyldigoxin and ouabain were assessed in [³H]-ouabain binding assays in the abse…