Interactions of lithium and protons with the sodium-proton exchanger of dog red blood cells

Passive movements of Li in dog red blood cells (RBC) ar like those of Na and protons in being stimulated by osmotic cell shrinkage and inhibited by amiloride. Li and protons have similar asymmetrical effects on Na-H exchange. When the intracellular fluid is made rich in Li or protons, Na-H exchange is stimulated. When the extracellular fluid is enriched in Li or protons, Na-H exchange is inhibited. In the case of protons, these effects can override alterations in driving force that are created by the experimental conditions. For example, acidification of the cytoplasm stimulates outward Na movements, while acidification of the medium inhibits Na efflux. Thus, protons (and, by analogy, Li) can interact with the Na-H exchanger not only as substrates but also as modulators. In previous experiments, the only way to activate the Na-H exchanger in dog RBC was to shrink the cells in hypertonic media. The influences of Li or protons, however, are so strong as to preempt the volume effects, so that the pathway can be activated even in swollen cells and deactivated in shrunken ones.