Studies on the lithium transport across the red cell membrane

Abstract

In studies on Li⁺ net-transport across the human red cell membrane following results were obtained: In K⁺- and Na⁺-free choline chloride media, Li⁺ is transported into the erythrocytes against an electrochemical gradient. This Li⁺ uphill transport as well as Li⁺ downhill transport into the cells is inhibited by ouabain, ATP-depletion, and by external K⁺ and Na⁺. The effects of K⁺ and Na⁺ are relieved at high Li⁺ concentrations. Ouabain-sensitive Li⁺ uptake, determined at 10 mM external Na⁺, does not obey simple Michaelis-Menten kinetics and exhibits a maximum at about pH 7. Ouabain-resistant Li⁺ downhill transport into erythrocytes increases with rising pH. It is comprised of a saturating component and a component linearly dependent on external Li⁺. The linear component is partly inhibited by dipyridamole and accelerated by bicarbonate. The bicarbonate effect can be completely blocked by dipyridamole, phlorizin and phenylbutazone. Li⁺ release is not inhibited by ouabain, ATP-depletion and external K⁺. It increases with external Na⁺ concentration, tending to saturate at 150 mM Na⁺. Na⁺-independent Li⁺ release is stimulated by bicarbonate. It is concluded that ouabain-sensitive Li⁺ uptake is mediated at the K⁺-site(s) of the Na⁺−K⁺ pump. Li⁺, K⁺ and Na⁺ appear to compete for a common site (or sites). The stimulation of Li⁺ transfer by bicarbonate and the inhibition by dipyridamole suggest a participation of anoonic species in ouabain-resistant Li⁺ transfer. The Na⁺-dependent Li⁺ release and the “saturating component” of Li⁺ uptake are ascribed to the Na⁺-dependent Li⁺ countertransport system.