scholarly journals Potassium-regulated distal tubule WNK bodies are kidney-specific WNK1 dependent

2018 ◽  
Vol 29 (4) ◽  
pp. 499-509 ◽  
Author(s):  
Cary R. Boyd-Shiwarski ◽  
Daniel J. Shiwarski ◽  
Ankita Roy ◽  
Hima N. Namboodiri ◽  
Lubika J. Nkashama ◽  
...  
Keyword(s):  
Distal Tubule ◽  
Terminal Exon ◽  
Dietary Potassium ◽  
Evolutionarily Conserved ◽  
Wnk Kinases ◽  
Ribosomal Protein L22 ◽  
Distal Tubules ◽  
Renal Tubular ◽  
Potassium Loading

With-no-lysine (WNK) kinases coordinate volume and potassium homeostasis by regulating renal tubular electrolyte transport. In the distal convoluted tubule (DCT), potassium imbalance causes WNK signaling complexes to concentrate into large discrete foci, which we call “WNK bodies.” Although these structures have been reported previously, the mechanisms that drive their assembly remain obscure. Here, we show that kidney-specific WNK1 (KS-WNK1), a truncated kinase-defective WNK1 isoform that is highly expressed in the DCT, is critical for WNK body formation. While morphologically distinct WNK bodies were evident in the distal tubules of mice subjected to dietary potassium loading and restriction, KS-WNK1 knockout mice were deficient in these structures under identical conditions. Combining in vivo observations in kidney with reconstitution studies in cell culture, we found that WNK bodies are dynamic membraneless foci that are distinct from conventional organelles, colocalize with the ribosomal protein L22, and cluster the WNK signaling pathway. The formation of WNK bodies requires an evolutionarily conserved cysteine-rich hydrophobic motif harbored within a unique N-terminal exon of KS-WNK1. We propose that WNK bodies are not pathological aggregates, but rather are KS-WNK1–dependent microdomains of the DCT cytosol that modulate WNK signaling during physiological shifts in potassium balance.

Localization of diuretic action in microperfused rat distal tubules: Ca and Na transport

1985 ◽  
Vol 248 (4) ◽  
pp. F527-F535 ◽  
Author(s):  
L. S. Costanzo
Keyword(s):  
Distal Tubule ◽  
Maximal Concentration ◽  
Na Transport ◽  
Tubule Cell ◽  
Ca Transport ◽  
Site Of Action ◽  
Distal Tubules ◽  
Sites Of Action ◽  
Distal Site

Experiments were performed in rats to examine the distal site of action of thiazide diuretics and the additive hypocalciuric properties of thiazides and amiloride. In clearance experiments, the maximal natriuretic and hypocalciuric dose of chlorothiazide was established. When amiloride was added, there was further augmentation of Ca reabsorption (P less than 0.025) but no additional natriuresis. Amiloride blunted thiazide-induced kaliuresis (P less than 0.001). Localization of the thiazide effect was studied in early and late distal tubules microperfused in vivo with control and thiazide-containing solutions. The maximally effective luminal drug concentration, 5 X 10(-4) M, inhibited Na transport (P less than 0.001) and enhanced Ca transport (P less than 0.01) in the early distal segments; late segments were on the average unaffected. It is suggested that thiazides interact with the distal convoluted tubule cell, whose predominant location is the early distal tubule. In two long distal tubules, with early and late segments, a maximal concentration of chlorothiazide increased Ca transport and decreased Na transport. Addition of 10(-5) M amiloride caused an additional increment in Ca reabsorption. As amiloride's action is located in the late distal tubule, it is suggested from these experiments that a basis for additive hypocalciuric actions of thiazides and amiloride is separate sites of action in the distal tubule.

Active potassium absorption by the renal distal tubule

1992 ◽  
Vol 262 (3) ◽  
pp. F488-F493 ◽  
Author(s):  
M. D. Okusa ◽  
R. J. Unwin ◽  
H. Velazquez ◽  
G. Giebisch ◽  
F. S. Wright
Keyword(s):  
Distal Tubule ◽  
Sprague Dawley ◽  
Direct Demonstration ◽  
Sprague Dawley Rats ◽  
Potassium Flux ◽  
Low Potassium ◽  
Potassium Absorption ◽  
Transepithelial Voltage ◽  
Distal Tubules

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.

Distal tubular acidification in the remnant kidney

1990 ◽  
Vol 258 (1) ◽  
pp. F69-F74 ◽  
Author(s):  
R. T. Kunau ◽  
K. A. Walker
Keyword(s):  
Distal Tubule ◽  
Relative Increase ◽  
Control Group ◽  
Acid Base ◽  
Urine Ph ◽  
Base Parameters ◽  
Distal Tubules ◽  
The Difference ◽  
Remnant Kidney

The present studies examined the effect of three-fourths nephrectomy on the rate of acidification, i.e., total CO2 (tCO2) absorption (JtCO2) in the superficial distal tubule of the rat. Total glomerular filtration rate following three-fourths nephrectomy was 1.29 +/- 0.06 vs. 3.29 +/- 0.08 ml/min in sham controls, P less than 0.001. Systemic acid-base parameters were the same in both groups, but urine pH was lower in nephrectomized rats. In vivo microperfusion with identical isohydric solutions revealed that the JtCO2, fluid absorption (Jv), lumen-negative transepithelial potential difference (VT) were all significantly greater in the distal tubule of remnant kidneys. As the relative increase in Jv exceeded JtCO2, the perfusate tCO2 concentration increased markedly in remnant kidney distal tubules from 30.3 +/- 0.59 to 39.9 +/- 1.73 mM. To determine if the increase in tCO2 concentration accounted for the difference in JtCO2, a second control group was studied using a perfusate tCO2 concentration of 39.6 +/- 0.79 mM. Distal tubular JtCO2, Jv, and VT were significantly less in this control group than in the remnant kidney group. In separate studies, 10(-4) M amiloride was added to the perfusate used in remnant kidneys and controls studied with the elevated perfusate tCO2 concentration. The addition of 10(-4) M amiloride to the perfusate reduced VT and JtCO2. At identical values for VT, JtCO2 was higher in the distal tubule of remnant kidneys than in controls. We conclude the following. 1) The rate of acidification is increased in the distal tubule of remnant kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo adaptation of bicarbonate reabsorption by rat distal tubules during acid loading

1994 ◽  
Vol 267 (5) ◽  
pp. F737-F747 ◽  
Author(s):  
D. Z. Levine ◽  
M. Iacovitti ◽  
S. Buckman ◽  
D. Vandorpe ◽  
V. Harrison ◽  
...  
Keyword(s):  
Water Flux ◽  
Distal Tubule ◽  
Bafilomycin A1 ◽  
Bicarbonate Reabsorption ◽  
Distal Tubules ◽  
Acid Loading ◽  
Fasted Rats ◽  
Predominant Effect ◽  
Stimulation Of

We carried out in vivo microperfusion experiments in acid-loaded rats to characterize the adaptive response of the unidirectional components secretory flux (Jsec) and reabsorptive flux (Jreab)] of distal tubule bicarbonate reabsorption and to test the hypothesis that Jreab is dependent on bafilomycin A1-sensitive H(+)-adenosinetriphosphatase activity. During 18 h of severe acidosis there was a significant decrease in Jsec (-15 +/- 3 vs. -38 +/- 5 pmol.min-1.mm-1, P < 0.05) and a significant increase in Jreab (37 +/- 6 vs. 0 +/- 5 pmol.min-1.mm-1, P < 0.05), which was insensitive to 10(-5) M bafilomycin A1, 10(-5) M Sch-28080, and 3 mM amiloride. After 3 days of acid loading, these same inhibitors reduced Jreab by approximately 60%. However, when water flux was completely inhibited by isosmotic perfusion, a significant Jreab (15 +/- 2 pmol.min-1.mm-1) resistant to 10(-5) M bafilomycin A1 persisted, as in severe acidosis. In reabsorbing distal tubules of overnight-fasted rats, Sch-28080 elicited no inhibition, whereas bafilomycin A1 and amiloride had significant effects (28 +/- 5, 24 +/- 4, respectively, vs. 50 +/- 4 pmol.min-1.mm-1 for fasted rats, P < 0.05). Thus, although Jsec is reduced in the transition from mild to severe metabolic acidosis of 18-h duration, the predominant effect is a stimulation of bafilomycin A1-resistant Jreab.

In vivo modulation of rat distal tubule net HCO3 flux by VIP, isoproterenol, angiotensin II, and ADH

1994 ◽  
Vol 266 (6) ◽  
pp. F878-F883 ◽  
Author(s):  
D. Z. Levine ◽  
M. Iacovitti ◽  
S. Buckman ◽  
V. Harrison
Keyword(s):  
Angiotensin Ii ◽  
Vasoactive Intestinal Peptide ◽  
Distal Tubule ◽  
Similar Response ◽  
Acid Base Balance ◽  
Base Balance ◽  
Distal Tubules ◽  
In Vivo Effects ◽  
Fasted Rats

To examine the in vivo effects of agonists reported to influence bicarbonate flux (JtCO2), microperfusion experiments were carried out on distal tubules of normally fed or overnight-fasted rats. As we previously reported, distal tubules from fed rats reabsorbed no bicarbonate, whereas overnight-fasted rats consistently reabsorbed bicarbonate (JtCO2 10 +/- 3 pmol.min-1.mm-1; P < 0.01). Vasoactive intestinal peptide and isoproterenol infused intravenously (7.3 and 4.0 micrograms.kg-1.h-1, respectively) in fasted rats suppressed JtCO2 and, in the case of vasoactive intestinal peptide, elicited net bicarbonate secretion (JtCO2 -10 +/- 2 and -4 +/- 4 pmol.min-1.mm-1, respectively). In fed rats, angiotensin II infused at a rate of 1.2 micrograms.kg-1.h-1 stimulated bicarbonate reabsorption (JtCO2 16 +/- 3 pmol.min-1.mm-1), while antidiuretic hormone infused at 0.024 micrograms.kg-1.h-1 elicited a similar response (17 +/- 4 pmol.min-1.mm-1), both values being significantly different from control. These results, therefore, demonstrate for the first time that these agonists can modulate JtCO2 at the distal tubule site in vivo and therefore may be potential regulators of systemic acid-base balance.

Chloride-dependent potassium secretion in early and late renal distal tubules

1987 ◽  
Vol 253 (3) ◽  
pp. F555-F562 ◽  
Author(s):  
H. Velazquez ◽  
D. H. Ellison ◽  
F. S. Wright
Keyword(s):  
Interstitial Fluid ◽  
Diffusion Mechanism ◽  
Chloride Concentration ◽  
Distal Tubule ◽  
Distal Segment ◽  
Collecting Tubule ◽  
Potassium Secretion ◽  
Series Of Experiments ◽  
Distal Tubules

Potassium transport by subsegments of the rat surface distal tubule was studied using a modified in vivo microperfusion method. The nephron segments between 14 and 38% and between 62 and 83% of total distal length distance between macula densa region and confluence of tubule with another) were perfused separately. The first of these two segments is composed primarily of distal convoluted tubule (DCT) cells; the more distal segment is made up primarily by initial collecting tubule (ICT) epithelium. Experiments were performed to measure potassium secretion via two pathways: a diffusion mechanism driven by a favorable electrochemical gradient for potassium, and a cotransport mechanism activated when lumen chloride concentration is low. In a first series of experiments, both the DCT and the ICT secreted potassium when perfused with an artificial control solution resembling fluid normally present at the beginning of the distal tubule. Absolute rates of potassium secretion were higher in the ICT than in the DCT. Decreasing lumen Cl concentration stimulated potassium secretion more in the ICT than in the DCT. In a second series of experiments, the subsegments were perfused with a solution in which ion concentrations were raised to levels found in interstitial fluid. Under these circumstances, potassium secretion was lower in both segments. Decreasing lumen Cl concentration resulted in higher rates of potassium secretion in the DCT than those seen in the first series with low chloride; rates of potassium secretion in the ICT were as high as in the first series.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of graded solute diuresis on renal tubular sodium transport in the rat

1975 ◽  
Vol 228 (4) ◽  
pp. 1262-1268 ◽  
Author(s):  
RN Khuri ◽  
N Strieder ◽  
M Wiederholt ◽  
G Giebisch
Keyword(s):  
Sodium Transport ◽  
Distal Tubule ◽  
Sodium Concentration ◽  
Sodium Reabsorption ◽  
Saline Loading ◽  
Intravenous Saline ◽  
Distal Tubules ◽  
Tubular Flow ◽  
Renal Tubular ◽  
Saline Solutions

Sodium transport was studied across proximal and distal tubules of rats undergoing progressive intravenous loading with either isomotic saline or urea (200 mosmol)-saline (100 mosmol) solutions. Free-flow as well as recollection micropuncture techniques were used, and tubular fluid (TF) samples were analyzed for inulin-14C and sodium (Na). With administration of progressively larger intravenous saline loads, the delivery of fluid and sodium into the distal tubule rose. Concomitantly, the normally observed decline of tubular sodium concentrations along the distal tubule became attenuated until it was abolished at the highest infusion rates of saline solutions. Absolute reabsorption rates of Na across the distal tubule increased in proportion to tubular flow rate, and no tubular maximum (Tm) was observed. It is suggested that the delivery of increased amounts of sodium to the normally unsaturated later parts of the distal tubule and the elevated tubular sodium concentration after saline loading account for the observed stimulation of distal tubular net sodium transport. The extent of transport stimulation is also subject to control by the amount of urea accumulation along the distal tubule. As the latter declines, sodium reabsorption is proportionately enhanced.

Upregulation of H+-ATPase in the distal nephron during potassium depletion: structural and functional evidence

1998 ◽  
Vol 275 (6) ◽  
pp. F878-F884 ◽  
Author(s):  
Matthew A. Bailey ◽  
Robert M. Fletcher ◽  
David F. Woodrow ◽  
Robert J. Unwin ◽  
Stephen J. Walter
Keyword(s):  
Atpase Activity ◽  
Apical Membrane ◽  
Staining Pattern ◽  
Distal Tubule ◽  
Potassium Depletion ◽  
Intercalated Cells ◽  
Distal Nephron ◽  
Sprague Dawley ◽  
Dietary Potassium

In the present study, we have investigated the effects of dietary potassium depletion on the activity and distribution of the H+-ATPase in the distal nephron of the Sprague-Dawley rat. H+-ATPase activity was assessed from the change in transepithelial potential difference ( V te) in response to bafilomycin A1 during perfusion of the late distal tubule in vivo, with solutions containing inhibitors of known ion channels. Bafilomycin A1 caused a negative deflection in V te in control animals, an effect that was significantly enhanced during potassium depletion ( P < 0.01). The distribution of H+-ATPase within the population of intercalated cells was assessed using a specific monoclonal antibody (E11). Hypokalemia was associated with a highly significant redistribution of the staining pattern ( P < 0.001), with an increase in the percentage of cells displaying immunoreactivity in the apical membrane. These results indicate that dietary potassium depletion increases electrogenic H+-ATPase activity in the rat distal tubule; this may be associated with increased insertion of pumps into the apical membrane.

Augmented bidirectional HCO3 transport by rat distal tubules in chronic alkalosis

1991 ◽  
Vol 261 (2) ◽  
pp. F308-F317 ◽  
Author(s):  
D. E. Wesson ◽  
G. M. Dolson
Keyword(s):  
Metabolic Alkalosis ◽  
Distal Tubule ◽  
Free Flow ◽  
Proton Secretion ◽  
Nephron Segment ◽  
Distal Tubules ◽  
And Control

Free-flow micropuncture studies show both augmented net HCO3 reabsorption in the distal tubule of rats with chronic metabolic alkalosis and higher HCO3 delivery to this nephron segment. The present studies in rats used in vivo microperfusion of surface distal tubules to investigate whether the augmented net reabsorption 1) was due to decreased HCO3 secretion and/or to increased proton secretion or 2) depended on the higher HCO3 delivery to the distal tubule. Artificial perfusates were designed to simulate in situ deliveries of HCO3 to the distal tubules of both alkalotic and control animals and to represent extremes of in situ Cl deliveries. Rather than being decreased, both measured and calculated HCO3 secretion were higher in the alkalotic animals for each perfusate used. Similarly, calculated proton secretion (difference between net HCO3 reabsorption and calculated HCO3 secretion) was higher for the alkalotic animals using each HCO3-containing perfusate. Augmented net HCO3 reabsorption by alkalotic animals was more clearly demonstrated using higher HCO3 deliveries and Cl-free perfusates. These studies demonstrate that both the reabsorptive and secretory components of net HCO3 transport are increased in the distal tubule of animals with chronic metabolic alkalosis.

Sodium and chloride transport in the large intestine of potassium-loaded rats

1986 ◽  
Vol 251 (2) ◽  
pp. G249-G252 ◽  
Author(s):  
M. E. Budinger ◽  
E. S. Foster ◽  
J. P. Hayslett ◽  
H. J. Binder
Keyword(s):  
Chloride Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Ringer Solution ◽  
Sodium Absorption ◽  
Chloride Absorption ◽  
Dietary Potassium ◽  
Potassium Secretion ◽  
Potassium Loading

Increased dietary potassium ("potassium loading") induces several adaptive changes in colonic function, including increased potential-dependent potassium secretion, active potassium secretion, and Na-K-ATPase activity, but does not alter net sodium absorption in vivo. To establish whether potassium loading stimulates active sodium transport, unidirectional, net sodium, and chloride fluxes were determined under voltage-clamp conditions across isolated rat distal colonic mucosa. In normal animals net sodium flux (JNanet), net chloride flux (JClnet) and short-circuit current (Isc) were 6.1 +/- 1.1, 8.4 +/- 1.0, and 0.7 +/- 0.1 mu eq X h-1. cm-2, respectively; potassium loading significantly increased JNanet and Isc by 4.9 +/- 1.4 and 3.5 +/- 0.7 mu eq X h-1 X cm-2, respectively, without changing JClnet. Amiloride (0.1 mM) inhibited the increases in JNanet and Isc produced by potassium loading. In Cl-free Ringer solution in normal animals JNanet was reduced to 0.6 +/- 0.3 mu eq X h-1 X cm-2. Potassium loading produced identical increases in JNanet and Isc, which were also completely inhibited by 0.1 mM amiloride. These studies establish that potassium loading induces amiloride-sensitive electrogenic sodium absorption without affecting electroneutral sodium-chloride absorption.

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