Adaptation of distal tubule and collecting duct to increased Na delivery. II. Na+ and K+ transport

1988 ◽  
Vol 255 (6) ◽  
pp. F1269-F1275 ◽  
Author(s):  
B. A. Stanton ◽  
B. Kaissling
Keyword(s):  
Tap Water ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Extracellular Fluid ◽  
Distal Tubule ◽  
Sodium Absorption ◽  
Transport Capacity ◽  
Volume Depletion ◽  
Osmotic Minipump ◽  
Sodium Uptake

This study was conducted to determine whether a chronic increase in sodium delivery to, and sodium uptake by, the distal tubule stimulates the transport capacity of this tubular segment. To increase the rate of sodium delivery to the distal tubule, furosemide (12 mg/day) was administered continuously to rats by osmotic minipump for 6 days. Volume depletion was prevented by giving the animals a drinking solution containing 0.8% NaCl and 0.1% KCl. Control animals were given vehicle (0.9% NaCl) by osmotic minipump and tap water to drink. All animals were adrenalectomized and given replacement doses of aldosterone (0.5 microgram.100 g-1.day-1) and dexamethasone (1.2 microgram.100 g-1.day-1) to eliminate changes in adrenal corticosteroid levels. Furosemide was withdrawn 12 h before sodium and potassium transport rates were measured in distal tubules by in vivo microperfusion. We found that increased sodium uptake dramatically enhanced the transport capacity of the distal tubule. Sodium absorption rose from 71.7 to 316.7 pmol.min-1.mm-1, and potassium secretion increased from 30.7 to 73.7 pmol.min-1.mm-1. This response was accompanied by an increase in cell and mitochondrial volume and by proliferation of the basolateral membrane of distal convoluted cells, connecting tubule cells, and principal cells in the distal tubule. We conclude that a chronic increase in sodium uptake by the distal tubule, independent of alterations in extracellular fluid volume and aldosterone levels, stimulates the transport capacity of this nephron segment in part by inducing specific alterations in cell ultrastructure.

Adaptation of distal tubule and collecting duct to increased sodium delivery. I. Ultrastructure

1988 ◽  
Vol 255 (6) ◽  
pp. F1256-F1268 ◽  
Author(s):  
B. Kaissling ◽  
B. A. Stanton
Keyword(s):  
Tap Water ◽  
Collecting Duct ◽  
Cell Structure ◽  
Basolateral Membrane ◽  
Distal Tubule ◽  
Cortical Collecting Duct ◽  
Volume Depletion ◽  
Membrane Area ◽  
Osmotic Minipump ◽  
Sodium Uptake

We examined the effects of a chronic increase in tubular sodium delivery on the structure of the distal convoluted tubule (DCT), connecting tubule (CNT), and cortical collecting duct of male Sprague-Dawley rats. Furosemide (12 mg/day) was administered by osmotic minipump for 6 days to increase the rate of sodium delivery to these segments and thereby stimulate sodium uptake. To prevent volume depletion, the furosemide-treated animals were given a drinking solution containing 0.8% NaCl and 0.1% KCl. Control animals were given vehicle (0.9% NaCl) by osmotic minipump and they drank tap water. Furosemide dramatically increased urinary fluid and sodium excretion and decreased urine osmolality threefold vs. control. Furosemide treatment was associated with an increase in epithelial volume of DCT cells, CNT cells, and principal cells and an increase in the basolateral membrane area and mitochondrial volume of each cell type. These alterations in cell structure were not related to changes in plasma aldosterone, glucocorticoid, or arginine vasopressin levels. We conclude that an increase in cell sodium uptake regulates the ultrastructure of the distal tubule.

Structural-functional relationships along the distal nephron

1986 ◽  
Vol 250 (1) ◽  
pp. F1-F15 ◽  
Author(s):  
K. M. Madsen ◽  
C. C. Tisher
Keyword(s):  
Atpase Activity ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Distal Tubule ◽  
Structural Heterogeneity ◽  
Apical Plasma Membrane ◽  
Thick Ascending Limb ◽  
Intercalated Cells ◽  
Principal Cells ◽  
Functional Relationships

The distal tubule, which includes the thick ascending limb (TAL), the macula densa, and the distal convoluted tubule (DCT), and the collecting duct are structurally heterogeneous, thus reflecting the functional heterogeneity that is also present. As the TAL ascends from medulla to cortex, the surface area of the apical plasma membrane increases while that of the basolateral membrane decreases. The structure of the DCT resembles that of the medullary TAL. An excellent correlation exists between structure, Na-K-ATPase activity, and NaCl reabsorptive capacity in the distal tubule. The collecting duct is subdivided into the initial collecting tubule (ICT), and cortical (CCD), outer medullary (OMCD), and inner medullary (IMCD) collecting ducts. Between the distal tubule and the collecting duct is a transition region termed the connecting segment or connecting tubule (CNT). Considerable structural heterogeneity exists along the collecting duct within the two major cell populations, the intercalated cells and the principal cells. In the CNT, the ICT, and the CCD, potassium loading and mineralocorticoids stimulate Na-K-ATPase activity and cause proliferation of the basolateral membrane of CNT cells and principal cells, thus identifying the cells responsible for mineralocorticoid-stimulated potassium secretion in these regions. Finally, at least two morphologically distinct populations of intercalated cells exist, types A and B. In the rat, type A predominates in the CNT and the OMCD and is believed to be responsible for H+ secretion, at least in the OMCD. Type B predominates in the CCD, where it may be involved in bicarbonate secretion.

Rat renal cortical OAT1 and OAT3 exhibit gender differences determined by both androgen stimulation and estrogen inhibition

2004 ◽  
Vol 287 (1) ◽  
pp. F124-F138 ◽  
Author(s):  
Marija Ljubojević ◽  
Carol M. Herak-Kramberger ◽  
Yohannes Hagos ◽  
Andrew Bahn ◽  
Hitoshi Endou ◽  
...  
Keyword(s):  
Gender Differences ◽  
Proximal Tubule ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Distal Tubule ◽  
Inhibitory Effect ◽  
Kidney Cortex ◽  
Thick Ascending Limb ◽  
Estradiol Treatment ◽  
Adult Rats

In rats, the secretion of p-aminohippurate (PAH) by the kidney is higher in males (M) than in females (F). The role of the major renal PAH transporters, OAT1 and OAT3, in the generation of these gender differences, as well as the responsible hormones and mechanisms, has not been clarified. Here we used various immunocytochemical methods to study effects of gender, gonadectomy, and treatment with sex hormones on localization and abundance of OAT1 and OAT3 along the rat nephron. Both transporters were localized to the basolateral membrane: OAT1 was strong in proximal tubule S2 and weak in the S3 segments, whereas OAT3 was stained in proximal tubule S1 and S2 segments, thick ascending limb, distal tubule, and in principal cells along the collecting duct. Gender differences in the expression of both transporters in adult rats (M > F) were observed only in the cortical tubules. OAT1 in the cortex was strongly reduced by castration in adult M, whereas the treatment of castrated M with testosterone, estradiol, or progesterone resulted in its complete restitution, further depression, or partial restitution, respectively. In adult F, ovariectomy weakly increased, whereas estradiol treatment of ovariectomized F strongly decreased, the expression of OAT1. The expression of OAT3 in the M and F cortex largely followed a similar pattern, except that ovariectomy and progesterone treatment showed no effect, whereas in other tissue zones gender differences were not observed. In prepubertal rats, the expression of OAT1 and OAT3 in the kidney cortex was low and showed no gender differences. Our data indicate that gender differences in the rat renal cortical OAT1 and OAT3 (M > F) appear after puberty and are determined by both a stimulatory effect of androgens (and progesterone in the case of OAT1) and an inhibitory effect of estrogens.

Renal potassium transport: morphological and functional adaptations

1989 ◽  
Vol 257 (5) ◽  
pp. R989-R997 ◽  
Author(s):  
B. A. Stanton
Keyword(s):  
Collecting Duct ◽  
Cell Structure ◽  
Basolateral Membrane ◽  
Distal Tubule ◽  
Morphological Evidence ◽  
Intercalated Cells ◽  
Principal Cells ◽  
K Secretion ◽  
K Concentration ◽  
And Function

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.

Mechanism underlying flow stimulation of sodium absorption in the mammalian collecting duct

2006 ◽  
Vol 291 (3) ◽  
pp. F663-F669 ◽  
Author(s):  
Tetsuji Morimoto ◽  
Wen Liu ◽  
Craig Woda ◽  
Marcelo D. Carattino ◽  
Yuan Wei ◽  
...  
Keyword(s):  
Flow Rate ◽  
Membrane Trafficking ◽  
Collecting Duct ◽  
Extracellular Fluid ◽  
Brefeldin A ◽  
Sodium Absorption ◽  
Laminar Shear Stress ◽  
Open Probability ◽  
Flow Rates ◽  
Fast Flow

Vectorial Na+ absorption across the aldosterone-sensitive distal nephron plays a key role in the regulation of extracellular fluid volume and blood pressure. Within this nephron segment, Na+ diffuses from the urinary fluid into principal cells through an apical, amiloride-sensitive, epithelial Na+ channel (ENaC), which is considered to be the rate-limiting step for Na+ absorption. We have reported that increases in tubular flow rate in microperfused rabbit cortical collecting ducts (CCDs) lead to increases in net Na+ absorption and that increases in laminar shear stress activate ENaC expressed in oocytes by increasing channel open probability. We therefore examined whether flow stimulates net Na+ absorption ( JNa) in CCDs by increasing channel open probability or by increasing the number of channels at the apical membrane. Both baseline and flow-stimulated JNa in CCDs were mediated by ENaC, as JNa was inhibited by benzamil. Flow-dependent increases in JNa were observed following treatment of tubules with reagents that altered membrane trafficking by disrupting microtubules (colchicine) or Golgi (brefeldin A). Furthermore, reducing luminal Ca2+ concentration ([Ca2+]) or chelating intracellular [Ca2+] with BAPTA did not prevent the flow-dependent increase in JNa. Extracellular trypsin has been shown to activate ENaC by increasing channel open probability, and we observed that trypsin significantly enhanced JNa when tubules were perfused at a slow flow rate. However, trypsin did not further enhance JNa in CCDs perfused at fast flow rates. Similarly, the shear-induced increase in benzamil-sensitive JNa in oocytes expressing protease resistance ENaC mutants was similar to that of controls. Our results suggest the rise in JNa accompanying increases in luminal flow rates reflects an increase in channel open probability.

Electroneutral NaCl transport by distal tubule: evidence for Na+/H+-Cl-/HCO3- exchange

1988 ◽  
Vol 254 (1) ◽  
pp. F80-F86 ◽  
Author(s):  
B. A. Stanton
Keyword(s):  
Basolateral Membrane ◽  
Distal Tubule ◽  
Sodium Absorption ◽  
Type I ◽  
Type Ii ◽  
Cell Type ◽  
Perfusion Fluid ◽  
Cellular Mechanisms ◽  
Nacl Transport ◽  
Sites Of Action

The mechanisms, of electrolyte transport by isolated and perfused late distal tubules of the salamander, Amphiuma, were investigated by electrophysiological and transport techniques. The tubules absorbed Na+, HCO3-, and Cl- but not K+. The transepithelial voltage (VT) was not different from zero. Amiloride (10(-3) M) in the perfusion fluid reduced sodium absorption by 43% and HCO3- absorption by 49% without changing VT. This and previous data are consistent with the presence of a Na+/H+ antiporter in the apical membrane. Hydrochlorothiazide (HCTZ, 10(-4) M) in the perfusion fluid inhibited Na+ absorption by 48% but had no effect on HCO3- absorption or VT. Thus HCTZ reduced NaCl absorption. Intracellular microelectrode techniques were used to examine the cellular mechanisms of ion transport and sites of action of amiloride and HCTZ. Two cell types were identified by their electrophysiological properties. Neither amiloride nor HCTZ appreciably altered the electrical properties of cell type I, a cell previously identified as being involved in H+ secretion. In contrast, both diuretics hyperpolarized the basolateral membrane voltage (Vbl) of cell type II. Additional studies of cell type II showed that the removal of Cl- from the lumen hyperpolarized Vbl, as did the addition to the lumen of the Cl-/HCO3- exchange inhibitor 4,4'-diisothiocyanostilbene-2-2'-disulphonic acid. Finally, reducing the [HCO3-] of the lumen depolarized Vbl.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphological and physiological responses to aldosterone: time course and sodium dependence

1990 ◽  
Vol 259 (1) ◽  
pp. F88-F94 ◽  
Author(s):  
J. B. Wade ◽  
B. A. Stanton ◽  
M. J. Field ◽  
M. Kashgarian ◽  
G. Giebisch
Keyword(s):  
Time Course ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Cortical Collecting Duct ◽  
Sprague Dawley ◽  
Morphological Response ◽  
Membrane Area ◽  
Osmotic Minipump ◽  
Principal Cells ◽  
K Secretion

The time course and Na+ dependence of morphological responses to a physiological elevation of aldosterone were examined in the renal cortical collecting duct. Male Sprague-Dawley rats were adrenalectomized and given a basal replacement infusion of aldosterone and dexamethasone by osmotic minipump. The animals were given additional aldosterone by either intravenous infusion or by a second implanted osmotic minipump for either 5 h or 1, 3, 7, or 14 days. Animals were fed either a Na(+)-replete or a low-Na+ diet. After these treatments we conducted a morphometric analysis on kidneys processed for electron microscopy by standard techniques. Increased aldosterone induced detectable proliferation of the basolateral membrane of principal cells after 24 h. Basolateral membrane continued to increase rapidly through 3 days of exposure and thereafter at a modest rate. Cell area and the surface density of the basolateral membrane were also increased by aldosterone treatment. The morphological response to aldosterone was markedly inhibited by maintaining animals on a low-Na+ diet. Acute exposure to elevated aldosterone levels (5 h) increased K+ secretion by principal cells without alterations in basolateral membrane area. Chronic (greater than 24 h) exposure to aldosterone induces morphological adaptations that are accompanied by further elevations in K+ secretion.

Thiazide-sensitive sodium chloride cotransport in early distal tubule

1987 ◽  
Vol 253 (3) ◽  
pp. F546-F554 ◽  
Author(s):  
D. H. Ellison ◽  
H. Velazquez ◽  
F. S. Wright
Keyword(s):  
Sodium Transport ◽  
Chloride Transport ◽  
Collecting Duct ◽  
Distal Tubule ◽  
Sodium Absorption ◽  
Transport Pathways ◽  
Luminal Membrane ◽  
Chloride Absorption ◽  
Distal Tubules

At least two pathways mediate sodium absorption across the luminal membrane of the renal distal tubule. One pathway is a conductive channel and the other appears to be a coupled Na-Cl cotransport pathway. The distal tubule comprises three segments: the distal convoluted tubule, the connecting tubule, and the initial collecting duct. To provide information about cellular locations of the proposed sodium transport pathways, we perfused early (14-38% of whole distal length) and late (61-83% of whole distal length) segments of whole distal tubules separately in vivo in anesthetized rats. When perfused with a solution that resembles fluid normally arriving at the distal tubule (75 mM Na, 68 mM Cl), rates of sodium absorption were similar in early and late segments (early 68 +/- 29.6, late 67 +/- 27.5 pmol X min-1 X mm-1). When perfused with a solution that resembles interstitial fluid (148 mM Na, 110 mM Cl), sodium transport was significantly higher in early than in late segments (276 +/- 28.4 vs. 113 +/- 29.7 pmol X min-1 X mm-1). Chlorothiazide (10(-3) M), which blocks sodium and chloride absorption in whole distal tubules, reduced sodium and chloride transport to zero in early distal tubules but had no significant effect in late distal tubules. Removing all chloride from perfusion solutions reduced sodium transport in early but not late distal segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic acidosis has dual effects on sodium handling by rat kidney

2006 ◽  
Vol 291 (2) ◽  
pp. F322-F331 ◽  
Author(s):  
Somia Faroqui ◽  
Sulaiman Sheriff ◽  
Hassane Amlal
Keyword(s):  
Metabolic Acidosis ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Distal Tubule ◽  
Protein Abundance ◽  
Water Control ◽  
Volume Depletion ◽  
Serum Aldosterone ◽  
Access To Water ◽  
Sodium Handling

Chronic metabolic acidosis (CMA) is associated with decreased NaCl reabsorption in the proximal tubule (PT). However, the effect of CMA on Na+ transport in the distal tubule (DT) and collecting duct (CD) is poorly understood. Rats were placed in metabolic cages and had access to water (control), 0.28 M NH4Cl, or 0.28 M KCl solutions in a pair-feeding protocol for 5 days (5d). Metabolic acidosis developed within 24 h in NH4Cl-, but not in KCl-loaded rats. Interestingly, NH4Cl- but not KCl-loaded rats exhibited a significant natriuresis after 24 h of treatment. Urinary Na+ excretion increased from 1.94 to 2.97 meq/24 h ( P < 0.001) and returned to below baseline level (1.67 meq/l) after 5d of CMA. The protein abundance of the cortical Na-Cl cotransporter (NCC) remained unchanged at 24 h, but increased significantly ( P < 0.01) after 5d of CMA. The protein abundance of α-, β-, and γ-subunits of the epithelial Na+ channel (ENaC) in the cortex decreased sharply during the first 24 h and then returned to baseline levels after 5d of CMA. Interestingly, Sgk1 expression decreased after 24 h (−31%, P < 0.05) and then returned to baseline after 5d of CMA. Nedd4–2 expression was not altered during CMA. CMA enhanced serum aldosterone levels by 54% and increased the expression of aldosterone synthase in the adrenal gland by 134% after 5d of CMA. In conclusion, metabolic acidosis has dual effects on urinary Na+ excretion. The early natriuresis results from decreased Na+ reabsorption in the PT and Sgk1-related decreased ENaC activity in the DT and CD. Aldosterone-induced upregulation of NCC, Sgk1, and ENaC likely contributes to the antinatriuretic phase of metabolic acidosis. This adaptation prevents Na+ wasting and volume depletion during chronic acid insult.

Regulation of renal ion transport and cell growth by sodium

1989 ◽  
Vol 257 (1) ◽  
pp. F1-F10 ◽  
Author(s):  
B. A. Stanton ◽  
B. Kaissling
Keyword(s):  
Cell Growth ◽  
Epithelial Cells ◽  
Basolateral Membrane ◽  
Extracellular Fluid ◽  
Sodium Concentration ◽  
Intracellular Sodium ◽  
Sodium Efflux ◽  
Renal Epithelial Cells ◽  
Sodium Uptake ◽  
Cell Growth And Proliferation

Intracellular sodium has been implicated in a variety of cellular processes including regulation of Na+-K+-ATPase activity, mitogen-induced cell growth, and proliferation and stimulation of Na+-K+-ATPase by aldosterone. In renal epithelial cells a rise in sodium uptake across the apical membrane increases intracellular sodium concentration, which in turn stimulates the turnover rate of Na+-K+-ATPase and thereby enhances sodium efflux across the basolateral membrane. A prolonged increase in sodium uptake causes dramatic hypertrophy and hyperplasia and a rise in the quantity of Na+-K+-ATPase in the basolateral membrane. These structural and functional changes occur in the kidney in the absence of alterations in plasma aldosterone and vasopressin levels. Several mitogens induce growth and proliferation by initiating a cascade of events, which include a rise in intracellular sodium. Accordingly, an increase in the sodium concentration within renal epithelial cells may elicit a “mitogen-like” effect by initiating the cascade at the sodium step, even in the absence of a mitogen. A rise in cell sodium may also stimulate the production of autocrine growth factors that directly or indirectly regulate cell growth and proliferation, by modifying the response to mitogens or to changes in the ionic composition of the extracellular fluid. In this review we will examine the evidence that supports a role for intracellular sodium in regulating these cellular events in renal epithelial cells.

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