Influence of extracellular K+ concentration on the time-course of Na+/K+-ATPase inhibition by cardiac glycosides with fast and low binding kinetics.
The magnitude of the K+ antagonism of cardiac glycoside binding to Na+/K+-ATPase prepared from porcine heart, was estimated from the enzyme activities determined in the presence of different concentrations of K+ ([K+]), ouabain, and alpha-methyl-digitoxigenin-glucoside, the latter showing a 30 fold greater dissociation rate than ouabain. An increase of [K+] (3-20 mmol/l) prolonged the half-lives of Na+/K+-ATPase inhibition and caused a rightward shift of the cardiac glycoside's dose-response curves by the same factor, almost maximal (4 fold) at 14 mmol/l K+. These data could be verified from the cardiac glycoside-elevated intravesicular Na+ concentrations of rat brain vesicles. These concentrations declined rapidly in brain vesicles treated with alpha-methyl-digitoxigenin-glucoside but not with ouabain after K+ was increased from 3.5 to 14 mM. The results suggest that the magnitude of the K+ antagonism under physiological conditions is only limited by the lifespan of the cardiac glycoside-binding E2P enzyme conformation reduced by K+.
Gleitz
J
J
University Clinics Ulm, Institute of Naturheilkunde, Germany. johannes.gleitz@medizin.uni-ulm.de
Peters
M
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002301:Cardiac Glycosides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D007700:Kinetics; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013552:Swine
D002301:Cardiac Glycosides; D004791:Enzyme Inhibitors; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium