Chronic K-supplementation Decreases Myocardial [Na,K-ATPase] and Net K-uptake Capacity in Rodents

The effects of high K intake on plasma K, myocardial K content and Na,K-ATPase concentration and on myocardial K uptake during KCl infusion were evaluated in rodents. Myocardial Na,K-ATPase was quantified in crude homogenates by K-dependent pNPPase activity in rats, and in intact samples by3H-ouabain binding in guinea pigs. Na,K-ATPaseαisoform distribution was assessed by immunoblotting. Plasma K was monitored in anesthetized rats during intravenous infusion of 0.75 mmol KCl/100 g body weight/h. A significant increase in plasma K was observed after 2 days of K supplementation, 4.9±0.2 (mean± )v3.0±0.2 mmol/l in weight matched controls (P<0.01,n=5) and this difference remained stable. After 1 day, a significant myocardial K content increase was obtained, 86.2±3.0v76.7±1.9μmol/g wet weight (P<0.05,n=5); after 4 days myocardial K stabilized 4.9±1.2μmol/g wet weight above control level (P<0.05,n=5). From the 4th day, a significant decrease in myocardial K-dependent pNPPase activity was observed, 1.18±0.04v1.31±0.01μmol/min/g wet weight in weight matched controls (P<0.05,n=5); after 2 weeks the decrease was 29% (P<0.05,n=5), with a reduction inα1-isoform abundance by 24% (P<0.05,n=5), and a tendency to a decrease inα2of 10% ( ,n=5). The measurements were validated by3H-ouabain binding to myocardial samples from guinea pigs K-supplemented for 2 weeks, showing a decrease of 21% (P<0.05,n=5). During KCl infusion, the myocardial K content increase rate was reduced by 52% (P<0.05) in the K-supplemented rats. The observed effects of K-supplementation on plasma K, myocardial K content and myocardial K-dependent pNPPase activity were abolished within 2 days after reallocation to chow with normal K content. In conclusion, high K-intake is associated with significantly and reversible increased plasma and myocardial K content, and decreased myocardial Na,K-ATPase concentration and net myocardial K uptake capacity. Thus, the heart is protected from major increases in intracellular K concentrations during chronically-high K-intake.