Figure 1.

Lithium is reabsorbed in different segments of the renal tubule and in the collecting duct. Lithium is freely filtered in the glomerulus and subsequently reabsorbed by different nephron segments. In the proximal tubules, lithium is, to a minor extent, reabsorbed through the transcellular pathway, which likely involves NHE3 at the apical plasma membrane and NHE1 at the basolateral plasma membrane. In the distal tubules and collecting duct, transcellular lithium uptake from the prourine occurs through the ENaC, whereas NHE1 likely mediates the cellular efflux to the interstitium. In both the proximal tubule and thick ascending limb of Henle (TAL), lithium is reabsorbed in a paracellular fashion, which is driven by the generated transcellular luminal–positive electrical gradient. In the TAL, this gradient is accomplished by luminal K⁺ efflux by renal outer medullary K⁺ 2 (ROMK2); K⁺, Na⁺, and Cl⁻ influx b Na⁺/K⁺/2Cl^– cotransporter 2 (NKCC2); and basolateral extrusion by the Na⁺/K⁺-ATPase and ClC-Kb chloride channels (as indicated).