Efficiency of sodium transport in the thick ascending limb

Abstract

Thick ascending limb (TAL) cells are thought to transport Na+ efficiently owing to passive paracellular Na+ absorption. Transport efficiency is of particular importance in the outer medulla where O2 availability is limited by low blood flow. We used a mathematical model of TAL cells to estimate the efficiency of Na+ transport along the TAL, and to examine what determines transport efficiency. The TAL cell model includes all major solutes and transporters and channels, and is based on mass conservation and electroneutrality constraints. We analyzed TAL transport in cells with conditions relevant to the inner stripe of the outer medulla, the corticomedullary junction, and in the distal cortical TAL. At each location, we varied luminal [Na+] and [Cl−] and simulated a stop flow condition, where the luminal solute concentrations decrease to limiting, static‐head values. Na+ transport efficiency was calculated as the ratio of total net Na+ transport to transcellular Na+ transport. The results show that transport efficiency decreases as the transepithelial Na+ gradient increases. Based on predictions from countercurrent models, transport efficiency is predicted to be highest at the corticomedullary boundary where the transepithelial Na+ gradient is the smallest. As transepithelial Na+ gradient increases towards the deep inner stripe, transport efficiency decreases. Transport efficiency also decreases in the cortex as the luminal ion concentrations approach static head. Funded by NIH Grants SC1GM084744 and DK42091 and NSF grant DMS‐0715021