Reduced Sodium Pump α 1 , α 3 , and β 1 -Isoform Protein Levels and Na + ,K + -ATPase Activity but Unchanged Na + -Ca 2+ Exchanger Protein Levels in Human Heart Failure

Abstract

Background−Cardiac glycosides initiate an increase in force of contraction by inhibiting the sarcolemmal sodium pump (Na+,K+-ATPase), thereby decreasing Ca2+ extrusion by the Na+-Ca2+ exchanger, which increases the cellular content of Ca2+. In patients with heart failure the sensitivity toward cardiac glycosides is enhanced. Methods and Results−Because the inotropic effect of cardiac glycosides may be a function of the sodium pump and Na+-Ca2+ exchanger (NCE) expression levels, the present study aimed to investigate protein expression of both transporters (immunoblot with specific antibodies against the sodium pump catalytic α1-, α2-, α3-, and glycoprotein β1-isoforms and against NCE) in left ventricle from failing (heart transplantations, New York Heart Association class IV, n=21) compared with nonfailing (donor hearts, NF, n=22) human myocardium. The density of 3H-ouabain–binding sites (Bmax) and the Na+,K+-ATPase activity were also measured. In NYHA class IV, protein levels of Na+,K+-ATPase α1- (0.62±0...