Membrane molecular aspects of tubule solute transport.

During recent years studies with isolated plasma membranes in general and transport experiments with plasma-membrane vesicles in particular (Kinne, 1976) have provided important information on the transport systems and the driving forces involved in the solute transport of the renal proximal tubule. The results of these studies are compiled in Fig. 1. In principle two driving forces can be distinguished, ATP hydrolysis for primary active transport processes and the Na+ gradient for secondary active-transport processes; the corresponding transport systems are ion-dependent ATPases. and Na+-co-transport systems. Na/K-ATPase and Ca-ATPase are present only in the basal-lateral (contraluminal) plasma membranes of the proximal tubular epithelial cells, the luminal membrane is supposed to contain a HC03stimulatable Mg-ATPase. Na/K-ATPase is involved in the active extrusion of Na+ out of the cell, Ca-ATPase activity seems to be related to an ATP-dependent movement of Ca2+ across the contraluminal cell border and the HC03stimulatable Mg-ATPase is thought to represent an ATP-driven proton pump. Na+-co-transport systems are also distributed asymmetrically within the cellular plasma-membrane envelope: D-glucose, phosphate, L-lactate, neutral and basic amino acids are transported across the brush border membrane by Na+-co-transport systems, whereas their exit from the cell involves Na+ independent transport systems. Acidic amino acids on the other hand are taken up into the cell both from the luminal and the contraluminal side by Na+-dependent systems. For protons and Caz+ there exist, in addition to ATPases, Na+-exchange systems; a proton-Na+ exchange system is localized in the brush-border membranes and a Ca'+/ Na+ exchange system is localized in the basal-lateral plasma membranes. For the studies mentioned above it is important that the membranes (including their transport machinery) be left essentially unaltered by the purification procedures, so that the isolated sheets or vesicles reflect very closely the functions of the plasma membrane of the intact cell in uiuo. This goal places this area of investigation at the border line between the classical physiological approach, which wants to understand organ function