K depletion modifies the properties of Sch-28080-sensitive K-ATPase in rat collecting duct

Abstract

Two distinct Sch-28080-sensitive K-adenosine triphosphatases (K-ATPases) were previously described in the rat nephron: a ouabain-resistant K-ATPase (type I) present in collecting ducts (CD) and a ouabain-sensitive from (type II) located in proximal tubules (PT) and thick ascending limbs (TAL). In K-depleted rats, K-ATPase activity is increased in CD, whereas it is reduced in PT and TAL. Because expression of colonic H-K-ATPase is restricted to the CD of K-depleted rats, we hypothesized that K-ATPase from the CD of K-depleted rats might be different from types I and II. Indeed, type III K-ATPase displays higher sensitivities to ouabain and to Sch-28080 than type II, a lower sensitivity to Sch-28080 than type I, and, conversely to types I and II, it can be stimulated by Na+. Pharmacological differences between types II and III K-ATPases were confirmed by [3H]ouabain binding experiments. Thus the rat kidney expresses three K-ATPases that differ by their pharmacological and kinetic properties, their distribution profile along the nephron and their behavior during K depletion.

Calcium-sensing Receptor Stimulates Luminal K+-dependent H+ Excretion in Medullary Thick Ascending Limbs of Henle's Loop of Mouse Kidney

“…It was demonstrated that mRNA expression of colonic H + -K + -ATPase (HKAc), which is nominally inhibited by ouabain, is present at low levels in mTAL (Ahn et al 1996). On the basis of functional and pharmacological properties, H + -K + -ATPase activity has been detected by analysis of K + -ATPase activities in various microdissected tubule segments of the rat kidney with respect to sensitivity to inhibitors ouabain and Sch-28080 and response to potassium deletion (Younes-Ibrahim et al 1995;Buffin-Meyer et al 1997;Silver et al 1999 Stimulation of CaSR in the TAL significantly increases 20-HETE production, which inhibits activity of the apical ROMK (Wang et al 1996). However, ROMK channels are crucial for K + recycling in mTAL and generate the lumen-positive transepithelial potential that is essential for maintaining normal function of the Na + -K + -2Cl -cotransporter and paracellular divalent mineral resorption.…”

The Non-gastric H,K-ATPase Is Oligomycin-sensitive and Can Function as an H+,NH4+-ATPase

“…Moreover, one should realize that these studies were performed in intact cells, leaving the possibility of other transporters being involved and thus complicating correct interpretation of the results. In contrast to the above idea, Na ϩ was shown to compete with K ϩ for transport via the non-gastric H,KATPase in the rabbit collecting duct (15), whereas in the rat collecting duct Na ϩ was found to increase the activity of this enzyme in the absence of K ϩ (16). Finally, there are indications that this enzyme might be involved in NH 4 ϩ transport (17)(18)(19), although the direction of this transport is controversial.…”

“…Initially, the properties of non-gastric H,K-ATPase were investigated in situ or in crude membranes from rat distal colon (16,18,23). More recently, this enzyme has also been studied in several expression systems including Xenopus laevis oocytes (6, 24 -27), HEK 293 cells (14,28), and the baculovirus expression system (9,29).…”

Acid-Base Homeostasis

“…H 1 /K 1 -ATPases in the collecting duct include both the gastric form of H 1 /K 1 -ATPase and the colonic form of H 1 /K 1 -ATPase (42). On the basis of inhibitor studies, there may also be a third type of H 1 / K 1 -ATPase in the collecting duct (43,44). These transporters likely contribute to urine acidification under normal conditions but particularly during states of potassium depletion (42,44).…”