Expression of α isoforms of the Na,K-ATPase in human heart

Augmentation of ouabain sensitivity of rat liver Na/K‐ATPase by in vivo adenovirus‐mediated expression of the Na/K‐ATPase α2 subunit

“…The efficacy of the expressed al isoform to augment ouabain binding activity in vivo represents a further validation of the putative function of the al isoform as a high affinity receptor for cardiac glycosides. These findings are consistent with previous in vitro studies which suggested the al isoform as a major high affinity ouabain sensitive isoform [5,16,17]. It was interesting that total cellular Na/K-ATPase activity remained constant even when al activity was expressed using a constitutive promoter.…”

“…It was of interest to express the al cDNA Na/K-ATPase isoform and examine its in vivo function. Although active Na/K-ATPase has been successfully expressed in vitro in Xenopus oocytes, several mammalian cell lines, yeast, and insect cells using a variety of expression vectors [5,16,17], in vivo expression with these gene transfer systems has not been successful. This is the first study to demonstrate the feasibility of using recombinant adenovirus-mediated gene transfer to express a functional Na/ K-ATPase isoform in vivo and study its effects on Na/K-ATPase membrane activity.…”

“…cardiac glycosides) to alter pathophysiology. Expression of the a2 and/or a3 isoforms of Na/K-ATPase is lower in heart failure [10][11][12][13][14][15][16]. Since these are the ouabain sensitive Na/K-ATPase isoforms, their expression may be useful to treat heart failure.…”

“…Recent studies have demonstrated that endogenous expression of a2 and oc3 isoforms of Na/K-ATPase is down-regulated by hypertrophy, hypertension, and congestive heart failure in intact hearts of several species [10][11][12][13][14][15][16]. Ouabain induces cardiac immediate early gene expression at doses which only inhibit a2 and oc3 isoforms of Na/K-ATPase [17], demonstrating that ouabain binding to cc2 and cc3 isoforms plays an important role in ouabain-induced cardiac gene regulation in addition to its ionotropic effects.…”

Regional expression of sodium pump subunits isoforms and Na+-Ca++ exchanger in the human heart.

“…While there are no significant differences in ␣ or ␤ isoform subunits or Na ϩ -Ca ϩϩ exchanger pool sizes between the left and right ventricle or septum, there may be differences at the cellular level, e.g., conduction tissue vs. nonconducting tissue (13,44) or subcellular level in peripheral sarcolemma vs. T tubule membranes, as in the rat (5,45). ␣ subunit expression in the heart is variable among species: ␣1 is expressed ubiquitously, and neither ␣2 nor ␣3 are expressed in all hearts: adult rat and mouse express ␣1 and ␣2 (␣3 expression is primarily restricted to the neonatal heart), dog and ferret express ␣1 and ␣3, and sheep and guinea pig may express just ␣1 (reviewed in reference 12).…”