Effects of lithium and thallous ions on sodium pump activity in the guinea-pig heart and their relationship to the positive inotropic action.
It has recently been demonstrated that both Tl+ and Li+ produce concentration- and time-dependent positive inotropic effects in guinea-pig atrial preparations although Tl+ inhibits and Li+ stimulates isolated Na+,K+-ATPase in vitro. In order to elucidate the mechanism of the positive inotropic actions of these cations, the effects of Tl+ and Li+ on sodium pump activity were studied. Active 86Rb uptake in guinea-pig ventricular slices, an estimate of sodium pump activity, was highly sensitive to the inhibitory effect of the cardiac glycosides. Preincubation of slices with Tl+ caused a dose- and time-dependent inhibition of active 86Rb uptake. Similar concentration- and time-dependent inhibition of active 86Rb uptake was observed when Na+ in a Krebs-Henseleit solution was partially replaced with Li+. Lithium, however, stimulated a partially purified Na+,K+-ATPase in vitro. During heart slice incubation, Tl+ and Li+ accumulated in a time-dependent manner. This accumulation was not readily reversible when slices were transferred into Tl+- or Li+-free solutions. It appears that the inhibition of sodium pump activity is related to the positive inotropic action of these cations.
D000818:Animals; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D011868:Radioisotopes; D012413:Rubidium; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013793:Thallium / Q000494:pharmacology*
D011868:Radioisotopes; D008094:Lithium; D012964:Sodium; D013793:Thallium; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium