Distribution and function of classes of ATPases along the nephron

Abstract

In a review published in 1977, Sachs [1] concluded that studies on renal tissue have so far not shown the presence of any active pump mechanism other than Na,K-ATPase, and pointed out that transport of Na, K, H, Cl, and HCO 3 can be explained by various modes of direct or indirect coupling to Na,K-ATPase. In the intervening years a large body of information further established the crucial role of Na,K-ATPase in tubular electrolyte transport, while at the same time providing evidence for the presence of other transport ATPases in the kidney. In parallel, microdissection and microanalysis techniques have made possible the examination of metabolic and enzymatic processes in discrete tubule segments that revealed the remarkable biochemical heterogeneity of the nephron [2], much as in the recent past in vitro tubule microperfusion has demonstrated the axial heterogeneity of its transport processes [3, 4]. Given the functional specialization of different nephron segments, one can easily appreciate why studies of renal biochemistry with classical methods using tissue slices or homogenates are subject to the same kind of limitations as, for example, the analysis of kidney function with clearance techniques: Both provide information about the kidney as a whole, rather than about its component units. To understand nephron function, one has to study it in its subdivisions of interest; to evaluate the regulation and the role of ATPases in tubular transport, it is essential to examine the behavior of these enzymes in individual nephron segments, and first to delineate their location along the nephron. This paper reviews the nephron distribution and function of several classes of ATPase, with emphasis on the sodium- and potassium-activated adenosine triphosphatase (Na,K-ATPase), and including the calcium- and proton-ATPases, about which much less is known at this time.