Fig. 2.

Cell models illustrating the effects of the LNaHK diet on Na⁺ and K⁺ transport properties of the distal nephron. A and B: illustrations of the Na⁺ and K⁺ transport pathways of the early distal convoluted tubule (DCT1) and CNT/CCD of animals on a regular diet (A) or LNaHK diet (B). A: for mice on a regular diet, ENaC reabsorbs 50% more Na⁺ than the Na⁺-Cl⁻ cotransporter (NCC) in the distal nephron. Approximately 75% of the K⁺ transported on Na⁺-K⁺-ATPase is secreted into the lumen, and 25% is recycled across the basolateral membrane to yield a Na⁺ reabsorbed-to-K⁺ secreted ratio of 0.5. Cl⁻ is reabsorbed via pendrin to account for the charge balance with Na⁺ reabsorption. B: the high K⁺ intake or elevating P[K⁺] turns off NCC of the DCT1, increasing the delivery of Na⁺ to ENaC. Renal and plasma ANG II levels elevate in response to the low Na⁺ intake with an increase in ENaC open probability and activation of renal outer medullary K⁺ (ROMK) channels. Aldosterone (Aldo) has several effects to enhance K⁺ secretion, including increasing BK channels in ICs and Na⁺-K⁺-ATPase, ENaC, and ROMK channels in PCs. The elevated flow stimulates BK channels in PCs and ICs. To enhance the secreted K⁺-to-Na⁺ reabsorbed ratio greater than 2, it is hypothesized that Na⁺ is recycled via the Na⁺-dependent Cl⁻/HCO₃⁻ exchanger.