Interactions of cardiac glycosides with cells and membranes. IV. Effects of ouabain and bumetanide on 86Rb+ influx in cultured cardiac myocytes from neonatal rats.
Ouabain at nanomolar concentrations stimulates total Rb+ influx by 20 +/- 2% in monolayer cultures of myocytes which were either in physiologic ionic steady-state conditions ('control') or 'loaded with Na+' following exposure to K+-free medium. The ouabain-stimulated Rb+ influx was completely abolished by 0.1 mM bumetanide both in 'control' and in 'Na+-loaded' myocytes. Thus, addition of nanomolar concentrations of ouabain to myocytes markedly stimulate the bumetanide-sensitive Rb+ influx. This influx was increased up to 3- and 4-fold in 'control' and 'Na+-loaded' myocytes, respectively. Ouabain at nanomolar concentrations had no significant effect on the component of 86Rb+ influx which is inhibited by millimolar concentrations of ouabain (the so called 'ouabain-sensitive' or 'pump-mediated' Rb+ influx) in 'control' and 'Na+-loaded' cells. It is proposed that the increased rates of bumetanide-sensitive Rb+ influx are accompanied by an increased bumetanide-sensitive Na+ influx through the Na+/K+ cotransporter and thus to a transient increase in intracellular Na+ concentrations [Na+]i. The increase in [Na+]i, subsequently causes a transient elevation in [Ca2+]i via the Na+/Ca2+ exchanger and may be involved in the regulation of cardiac cells' contractility.
Heller
M
M
Institute of Biochemistry, Hebrew University, Hadassah Medical School, Jerusalem, Israel.
Hallaq
H
H
Panet
R
R
D000818:Animals; D000831:Animals, Newborn; D002034:Bumetanide / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004232:Diuretics / Q000494:pharmacology*; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D012414:Rubidium Radioisotopes; D012964:Sodium / Q000378:metabolism
D004232:Diuretics; D012414:Rubidium Radioisotopes; D002034:Bumetanide; D010042:Ouabain; D012964:Sodium