Medline ® Abstracts for References 2,7,8

Maintenance of K+ homeostasis in mammals and amphibians depends primarily on the kidneys which excrete 95% of K+ ingested in the diet. The amount of K+ in the urine is determined by the rate of K+ secretion or absorption by the distal tubule and the collecting duct. When K+ intake is increased, K+ secretion rises. The mechanisms of K+ secretion by the distal tubule and collecting duct are so efficient that K+ intake can increase 20-fold with little or no increase in body K+ content or in plasma K+ concentration. Elevated K+ secretion by the distal tubule and collecting duct occurs in part because of an increase in the quantity of Na+-K+-adenosinetriphosphatase (Na+-K+-ATPase) and amplification of the basolateral membrane of principal cells. When dietary K+ intake is reduced, urinary K+ excretion falls, because K+ secretory mechanisms are suppressed and K+ absorptive mechanisms, residing in the distal tubule and collecting duct, are activated. Because a low-K+ diet is associated with hypertrophy of intercalated cells, it has been suggested that this cell type absorbs K+, possibly by an H+-K+-ATPase. In this review, I discuss the functional and morphological evidence that supports the view that principal cells secrete K+ and that intercalated cells absorb K+. In addition, some of the hormones and factors that are responsible for these changes in cell structure and function are discussed.

The present review summarizes recent functional and structural evidence indicating that the kidney possesses at least one and probably more than one isoform of a proton- and potassium-activated adenosinetriphosphatase (H-K-ATPase). Functional studies have examined in detail the mechanism of luminal acidification and K/Rb absorption by the outer medullary collecting duct (OMCD) from the inner stripe, a high-capacity distal site of urinary acidification. These studies indicate that the mechanism of proton secretion in this segment is similar to a model proposed for gastric acid secretion. Specifically, the profound effect of H-K-ATPase inhibitors or luminal K removal on net bicarbonate (HCO3) absorption indicates a major role for an H-K pump in luminal acidification by the OMCD. The importance of an H-K-ATPase is further supported by the finding that nanomolar concentrations of bafilomycin A1, which specifically inhibit vacuolar-type H-ATPase, have significantly smaller effects on net HCO3 absorption than do H-K-ATPase inhibitors. Studies on the perfused inner medullary collecting duct (IMCD) and cultured IMCD cells also suggest a significant role for H-K-ATPase in luminal acidification by the IMCD. Evidence has accrued from studies in the cortical CD and OMCD that the mechanism of H-K-ATPase-mediated luminal proton secretion differs under K-replete and K-restricted conditions. In K repletion, luminal K ions transported by the pump recycle back into the lumen by a Ba-sensitive mechanism. However, in K restriction, the mechanism of the H-K-ATPase involves luminal proton secretion and K absorption that is insensitive to luminal Ba and, by inference, apical K recycling. Moreover, in K restriction, K/Rb absorption is inhibited by basolateral Ba, indicating that the pump operates to reabsorb K/Rb across the epithelium. The structural evidence reviewed here indicates the presence of mRNA within the mammalian kidney that is either identical or highly homologous to mRNAs for gastric and putative colonic H-K-ATPase alpha-subunits and gastric H-K-ATPase beta-subunit. Localization of these transcripts by in situ hybridization demonstrates gastric alpha- and beta-subunit mRNAs in intercalated cells of both the cortical and medullary CD, principal cells of the CD, and IMCD cells. Additional studies in transgenic mice indicate that regulatory sequences upstream to the H-K-ATPase beta-subunit gene direct transcription in both gastric parietal cells and the renal CD.(ABSTRACT TRUNCATED AT 400 WORDS)

Maintenance of potassium homeostasis during potassium depletion appears to involve an active potassium absorptive mechanism in the distal nephron. Direct demonstration of such a pathway in the distal tubule of the rat has been lacking. The purpose of the current study was to examine the hypothesis that an ATP-dependent active transport mechanism plays a role in potassium absorption by the rat distal tubule. We utilized in vivo microperfusion techniques in Sprague-Dawley rats maintained on a regular diet of low-potassium diet for 3-4 wk. The effect of a selective inhibitor of the gastric H-K-adenosinetriphosphatase (ATPase) (Sch 28080, 0.1 mM) was tested in distal tubules of both groups of rats. Distal tubules of normal rats secreted potassium. Sch 28080 had no effect on this net potassium flux. In contrast, distal tubules of potassium-deficient rats absorbed potassium. Sch 28080 abolished this potassium absorption and produced a small hyperpolarization of the lumen-negative transepithelial voltage (VTE). The change in VTE can be explained by a concomitant increase in potassium concentration in the late distal tubule. These results are consistent with the presence of an H-K-ATPase in the distal tubule of potassium-deficient rats.