Function and structure of H-K-ATPase in the kidney

Abstract

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)

Cellular distribution of the potassium channel KCNQ1 in normal mouse kidney

“…Recent studies have demonstrated that KCNQ1 is also present in parietal cells (13), which was confirmed here, and is necessary for gastric acid secretion (10,34). Isoforms of H (1, 2, 28, 38, 43) and contribute to acid secretion, similar to the gastric parietal cell (44). The cooperation of an apical K ϩ channel with H ϩ -K ϩ -ATPase transport has been proposed in previous studies from our laboratory (44,46).…”

“…Isoforms of H (1, 2, 28, 38, 43) and contribute to acid secretion, similar to the gastric parietal cell (44). The cooperation of an apical K ϩ channel with H ϩ -K ϩ -ATPase transport has been proposed in previous studies from our laboratory (44,46). Under K ϩ -replete conditions, apical H ϩ -K ϩ -ATPase transport in the rabbit CCD is accompanied by apical K ϩ recycling, resulting in proton secretion without transepithelial K ϩ absorption (44,46).…”

Metabolic acidosis stimulates H+ secretion in the rabbit outer medullary collecting duct (inner stripe) of the kidney.

“…*Significantly different from basal condition, applying to the increase in H flux after incubation at pH 6.8. Ϫ 3 found that 35% of the rate was due to the P-type H These data differ somewhat from those of Wingo's laboratory (26,27,49), which show ‫ف‬ 70% of HCO flux is sensitive to inhibition of H ϩ ,K ϩ -ATPase, and only 30% to inhibition of the vacuolar H ϩ -ATPase. The results do agree in that the combination of inhibitors totally eliminates net HCO absorption (27), indicating that the vacuolar H ϩ -ATPase and the P-type H ϩ ,K ϩ -ATPase are the two main proton pumps in the OMCD of the inner stripe.…”

The Multifunctional Fish Gill: Dominant Site of Gas Exchange, Osmoregulation, Acid-Base Regulation, and Excretion of Nitrogenous Waste

“…For instance, mammalian renal epithelial cells have H ϩ -K ϩ -ATPases, as well as NHEs, V-ATPases, along their luminal membranes. These transporters are divided further into isoforms that are thought to function in different nephron segments and may be stimulated by different pH and/or electrolyte imbalances (257, 567,691,813,814). It has recently been demonstrated that a transcript homologous to an H ϩ -K ϩ -ATPase is expressed in the gills of elasmobranchs.…”