In order to identify the tubular sites responsible for the reduced fractional excretion of lithium (FELi) during potassium depletion, free-flow micropuncture was performed in anaesthetized rats that had been fed a low potassium (low-K+) diet or a control diet for 5-6 days. FELi in low-K+ rats was 0.09 +/- 0.02, compared with 0.25 +/- 0.01 in control animals. 2. Fractional water reabsorption in proximal convoluted tubules was enhanced in potassium-depleted rats. However, fractional lithium reabsorption was not. Consequently, the tubular fluid-to-plasma lithium concentration ratio at the late proximal convoluted tubule was raised in the low-K+ animals (1.50 +/- 0.03 vs. 1.18 +/- 0.02; P < 0.001). 3. Fractional lithium delivery to the early distal tubule in low-K+ rats (0.31 +/- 0.01) was similar to that in control animals (0.30 +/- 0.02). However, whereas in control rats there was no significant difference between early and late distal tubular deliveries of lithium, late distal fractional lithium delivery in the low-K+ group was reduced markedly (to 0.10 +/- 0.01). 4. Treatment of potassium-depleted rats with amiloride had no effect on lithium reabsorption in the proximal convoluted tubule or loop of Henle. However, fractional lithium delivery to the end of the distal tubule was increased slightly (to 0.15 +/- 0.02; P < 0.05) and FELi was increased substantially (to 0.22 +/- 0.01; P < 0.001). 5. It is concluded that two factors contribute to the reduced FELi seen in potassium-depleted rats: lithium reabsorption in the superficial distal tubules and amiloride-sensitive lithium reabsorption in the collecting ducts. The data also suggest heterogeneity with respect to lithium handling between superficial and deep nephrons during potassium depletion.
