Studies on the lithium transport across the red cell membrane. III. Factors contributing to the intraindividual variability of the in vitro Li+ distribution across the human red cell membrane.

1. Extracellular potassium bicarbonate, ouabain, dipyridamole and the Na+ distribution between red cells and plasma influence Li+ transport across the human red cell membrane. The significance of these parameters for the intraindividual variability of the steady-state ratio of external to internal Li+ was studied in vitro. 2. Elevation of external K+ in the physiological concentration range increases the steady-state distribution ratio Lie+/Lii+ indirectly by increasing the ratio Nae+/Nai+ through activation of the Na+-K+ pump, and directly by inhibiting ouabain-sensitive Li+ uptake. 3. A rise in bicarbonate concentration decreases the Li+ ratio directly by accelerating Li+ uptake through a leak, and indirectly by increasing the Na+ leak, thus reducing the Na+ ratio. 4. Dipyridamole blocks both bicarbonate effects. 5. Ouabain decreases the Na+ ratio and inhibits Li+ uptake by the Na+-K+ pump, thereby exerting two opposite effects on the Li+ distribution ratio. 6. The results confirm the previous observation that the steady-state Li+ distribution depends strongly on the Na+ distribution ratio, i-e., the driving force for Na+-dependent Li+ uphill countertransport. It is concluded that the Na+ distribution between red cells and plasma and the concentrations of K+ and bicarbonate in plasma need to be considered as factors influencing the in vivo Li+ distribution. However, the considerable interindividual differences of Li+ distribution cannot be ascribed to variations in these parameters.