The Feldberg Lecture 1976. Solute transport across epithelia: what can we learn from micropuncture studies in kidney tubules?

Epithelial transport covers an enormously wide field of research on tissues such as skin, intestine, salivary or sweat glands and kidney tubules which, on first view, seem to have little in common. However, despite the vast number of transport functions which these tissues perform, it appears that all operate on a relatively small number of general principles and it is my intention to describe some of those principles which we can discern. I will do so not by screening the literature for comparative aspects but by focussing mainly on one single epithelium, the rat kidney proximal tubule, and probing further and further into its properties. Our interest in this epithelium was twofold: (1) we knew that the proximal tubule plays a paramount role in the absorption of the glomerular filtrate and hence in the maintenance of the water and electrolyte balance of the body in man the proximal tubules absorb approximately 140 1. of tubular urine per day and (2) we have found that, with respect to its transport functions, renal proximal tubule may serve as an ideal model tissue for a group of epithelia (comprising among others, small intestine, gall-bladder, and choroid plexus), as well as possibly some endothelia, to which the well known frog skin model of transepithelial transport cannot be applied. These epithelia we have classified (Fromter & Diamond, 1972) as 'leaky epithelia' in contrast to the frog skin type 'tight epithelia' which have different transport properties and serve different functions in the body. I will come back to the distinction between tight and leaky epithelia below. A considerable disadvantage of the kidney tubules in transport studies is their small size. Rat proximal tubule has an outer diameter of 45 jtm and a lumen diameter of only 20 ,um (compare Fig. 1). The wall is formed of one layer of uniform cuboidal cells, with nuclei, vacuoles and a dense packing of mitochondria. The luminal cell membrane surface (brush border) and the basal cell membrane surface (basal labyrinth) are greatly amplified by microvilli or basal infoldings respectively. The gaps between neighbouring cells (lateral spaces) are closed near the luminal end by terminal bars (so-called tight junctions; see Fig. 9 below). To study solute and water transport across such tiny structures as renal tubules requires appropriate micropuncture and microanalytical techniques. Such techniques were initially developed between 1920 and 1930 for work with the bigger tubules of frog and Necturus kidney (Richards, 1929) and since then have been more and more