Reduced Myocardial Na+, K+-pump Capacity in Congestive Heart Failure Following Myocardial Infarction in Rats

We examined changes in expression and function of the cardiac Na+, K+-pump in a post-infarction rat model of hypertrophy and congestive heart failure (CHF). Myocardial infarction was induced by ligation of the left coronary artery in Wistar rats and hearts were obtained from animals with CHF and from sham operated rats after 6 weeks. In the CHF group the ratio of heart weight to body weight was 70% greater compared to sham (*P<0.05) and all left-ventricular end-diastolic pressures (LVEDP) were above 15 mmHg. The expression of theα1- andβ1-subunits (mRNA and protein) of the Na+, K+-pump was not significantly different in CHF and sham. As compared to sham theα2isoform, mRNA and protein levels were lower in CHF hearts by 25 and 55%, respectively, whereas theα3isoform mRNA was greater by 120% in CHF. Theα3protein was not detectable in sham, but a prominent band was seen in CHF. Cell volume of isolated cardiomyocytes was 30% larger in CHF. Cardiomyocytes containing the Na+sensitive fluorescent dye SBFI were loaded to an intracellular Na+concentration ([Na+]i] of about 140 m in a K+- and Mg2+-free medium (140 m Na+, free Ca2+of 10−8 ). To avoid back leak of Na+and to ensure no voltage effects on the Na+, K+-pump extracellular Na+was subsequently removed, and 6 m Mg2+was added to the superfusate, The Na+, K+-pump was then reactivated by 10 m Rb+. SBFI fluorescence ratio decreased mono-exponentially with a time constant (τ) of 191±15 s in sham (n=8) and 320±38 s in CHF (n=9) rats (P<0.01). These changes in fluorescence indicate that the maximum rate of decline of [Na+]ifrom 100 to 35 m was 39% (P<0.005) slower in CHF compared to sham, whereas maximum pump rate per cell was not significantly altered (9.0±0.7 fmol/s in sham and 7.1±0.7 fmol/s in CHF cells). The [Na+]iwhich caused 50% pump activation (k0.5) was also not altered in CHF (40 m in both groups). We conclude that the number of Na+, K+-pumps per cell was maintained in CHF, but an isoform switch of theα3- replacing theα2-isoform occurred. However, maximum Na+, K+-pump rate in terms of rate of change of [Na+]iwas significantly attenuated in CHF, most likely as a result of increased cell size.