Role of the furosemide-sensitive Na+/K+ transport system in determining the steady-state Na+ and K+ content and volume of human erythrocytes in vitro and in vivo.
To study the physiological role of the bidirectionally operating, furosemide-sensitive Na+/K+ transport system of human erythrocytes, the effect of furosemide on red cell cation and hemoglobin content was determined in cells incubated for 24 hr with ouabain in 145 mM NaCl media containing 0 to 10 mM K+ or Rb+. In pure Na+ media, furosemide accelerated cell Na+ gain and retarded cellular K+ loss. External K+ (5 mM) had an effect similar to furosemide and markedly reduced the action of the drug on cellular cation content. External Rb+ accelerated the Na+ gain like K+, but did not affect the K+ retention induced by furosemide. The data are interpreted to indicate that the furosemide-sensitive Na+/K+ transport system of human erythrocytes mediates an equimolar extrusion of Na+ and K+ in Na+ media (Na+/K+ "cotransport"), a 1:1 K+/K+ (K+/Rb+) and Na+/Na+ "exchange" progressively appearing upon increasing external K+ (Rb+) concentrations to 5 mM. The effect of furosemide (or external K+/Rb+) on cation contents was associated with a prevention of the cell shrinkage seen in pure Na+ media, or with a cell swelling, indicating that the furosemide-sensitive Na+/K+ transport system is involved in the control of cell volume of human erythrocytes. The action of furosemide on cellular volume and cation content tended to disappear at 5 mM external K+ or Rb+. The in vivo red cell K+ content was negatively correlated to the rate of furosemide-sensitive K+ (Rb+) uptake, and a positive correlation was seen between mean cellular hemoglobin content and furosemide-sensitive transport activity. The transport system possibly functions as a K+ and water-extruding mechanism under physiological conditions in vivo. The red cell Na+ content showed no correlation to the activity of the furosemide-sensitive transport system.
D001692:Biological Transport / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005665:Furosemide / Q000494:pharmacology*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
D006454:Hemoglobins; D010042:Ouabain; D005665:Furosemide; D012964:Sodium; D011188:Potassium