Cardiac Na+/Ca2+ exchange activity in patients with end-stage heart failure.
OBJECTIVE
The aim of the present study was to investigate the functional activity and expression of the sarcolemmal Na+/Ca2+-exchanger in the failing human heart.


METHODS
Left ventricular samples were taken from eleven patients with end-stage heart failure and six organ donors (normal controls). The Na+/Ca2+-exchanger activity was assessed by measuring Na+ gradient-induced 45Ca2+ transport into sarcolemmal vesicles of quantitatively collected crude membrane preparations. The abundance of the Na+/Ca2+-exchanger protein was determined by Western blot analysis using a specific antiserum and the results were normalized to myocyte specific beta-myosin heavy chain protein content.


RESULTS
In membrane preparations of failing human hearts, both the Na+ gradient-induced 45Ca2+ transport activity and the level of immunoreactive Na+/Ca2+-exchanger protein were increased (P < 0.01) by 87% and 160% compared to controls, respectively.


CONCLUSIONS
In human end-stage heart failure the increased sarcolemmal Na+/Ca2+-exchanger activity appears to be due to an elevated expression of this protein. An increase in the expression and activity of the Na+/Ca2+-exchanger in the failing human heart may be of important functional significance: while a resulting increase in Ca2+ extrusion across the sarcolemma may limit diastolic Ca2+ overload, a corresponding influx of Na+ may be associated with membrane depolarization and enhanced arrhythmogenesis if the Na+/Ca2+-exchanger operates primarily in the forward mode.
Reinecke
H
H
Universitatsklinik Freiburg, Kardiologie und Angiologie, Germany.
Studer
R
R
Vetter
R
R
Holtz
J
J
Drexler
H
H
D000328:Adult; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000378:metabolism; D003327:Coronary Disease / Q000150:complications / Q000378:metabolism; D046508:Culture Techniques; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium