The dual effect of sodium ion on the digitalis-sodium pump interaction.
Digitalis glycosides are specific inhibitors of the sodium pump. While their effects on isolated Na,K-ATPase, an enzymatic representation of the sodium pump, can be quantified easily and precisely, estimation of their effects on the sodium pump and evaluation of the physiological significance of sodium pump inhibition are complicated by several factors. In isolated Na,K-ATPase, the specific binding of cardiac glycosides observed in the presence of Mg2+ and ATP is stimulated by Na+. In intact myocardial cells, conditions which enhance Na+ influx, and hence the amount of Na+ to be transported by the sodium pump, such as stimulation at high frequencies, presence of monensin (a sodium ionophore), batrachotoxin or grayanotoxin I, enhance the glycoside binding to the sodium pump. In left atrial muscle preparations isolated from the guinea-pig heart and stimulated at 0.5 Hz, binding of ouabain to glycoside binding sites on Na,K-ATPase was eliminated by lowering the extracellular Na+ concentration from 145 to 27 mM, a condition reported to lower the intracellular Na+ concentration by more than 60%. When ouabain exposure of atrial muscle preparations was restricted to the quiescent period, glycoside binding to the sodium pump was minimal. Monensin, however, caused ouabain to bind to the sodium pump in quiescent preparations. These results indicate that glycoside binding to the sodium pump is enhanced by intracellular Na+. In addition to enhancing the glycoside binding to the sodium pump, an elevation of intracellular Na+ reduces the reserve capacity of the sodium pump and therefore increases the sensitivity of the myocardium to sodium pump inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001496:Batrachotoxins / Q000494:pharmacology; D001665:Binding Sites; D004071:Digitalis Glycosides / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008985:Monensin / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000378:metabolism; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014118:Toxins, Biological / Q000494:pharmacology
D001496:Batrachotoxins; D004071:Digitalis Glycosides; D004224:Diterpenes; D007473:Ion Channels; D014118:Toxins, Biological; D010042:Ouabain; D008985:Monensin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; C001311:grayanotoxin I