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-ATPase alpha isoform 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+/-s.e.m.)v 3.0+/-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+/-3.0v 76.7+/-1.9 micromol/g wet weight (P<0.05, n=5); after 4 days myocardial K stabilized 4.9+/-1.2 micromol/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+/-0.04v 1. 31+/-0.01 micromol/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 in alpha1-isoform abundance by 24% (P<0.05,n=5), and a tendency to a decrease in alpha2 of 10% (n.s.,n=5). The measurements were validated by 3H-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.