Versatility of NaCl transport mechanisms in the cortical collecting duct

2017 ◽  
Vol 313 (6) ◽  
pp. F1254-F1263 ◽  
Author(s):  
Aurélie Edwards ◽  
Gilles Crambert
Keyword(s):  
Collecting Duct ◽  
Type A ◽  
Transport Systems ◽  
Intercalated Cells ◽  
Cortical Collecting Duct ◽  
Type B ◽  
Cell Type ◽  
Acid Base ◽  
Nacl Transport ◽  
Principal Cells

The cortical collecting duct (CCD) forms part of the aldosterone-sensitive distal nephron and plays an essential role in maintaining the NaCl balance and acid-base status. The CCD epithelium comprises principal cells as well as different types of intercalated cells. Until recently, transcellular Na+ transport was thought to be restricted to principal cells, whereas (acid-secreting) type A and (bicarbonate-secreting) type B intercalated cells were associated with the regulation of acid-base homeostasis. This review describes how this traditional view has been upended by several discoveries in the past decade. A series of studies has shown that type B intercalated cells can mediate electroneutral NaCl reabsorption by a mechanism involving Na+-dependent and Na+-independent Cl−/[Formula: see text] exchange, and that is energetically driven by basolateral vacuolar H+-ATPase pumps. Other research indicates that type A intercalated cells can mediate NaCl secretion, through a bumetanide-sensitive pathway that is energized by apical H+,K+-ATPase type 2 pumps operating as Na+/K+ exchangers. We also review recent findings on the contribution of the paracellular route to NaCl transport in the CCD. Last, we describe cross-talk processes, by which one CCD cell type impacts Na+/Cl− transport in another cell type. The mechanisms that have been identified to date demonstrate clearly the interdependence of NaCl and acid-base transport systems in the CCD. They also highlight the remarkable versatility of this nephron segment.

scholarly journals Intercalated Cell Subtypes in Connecting Tubule and Cortical Collecting Duct of Rat and Mouse

1999 ◽  
Vol 10 (1) ◽  
pp. 1-12 ◽  
Author(s):  
JIN KIM ◽  
YOUNG-HEE KIM ◽  
JUNG-HO CHA ◽  
C. CRAIG TISHER ◽  
KIRSTEN M. MADSEN
Keyword(s):  
Plasma Membrane ◽  
B Cells ◽  
Collecting Duct ◽  
Type A ◽  
Band 3 ◽  
Intercalated Cells ◽  
Cortical Collecting Duct ◽  
Type B ◽  
Intercalated Cell ◽  
Basolateral Plasma Membrane

Abstract. At least two populations of intercalated cells, type A and type B, exist in the connecting tubule (CNT), initial collecting tubule (ICT), and cortical collecting duct (CCD). Type A intercalated cells secrete protons via an apical H+ - ATPase and reabsorb bicarbonate by a band 3-like Cl-/HCO3- exchanger, AE1, located in the basolateral plasma membrane. Type B intercalated cells secrete bicarbonate by an apical Cl-/HCO3- exchanger that is distinct from AE1 and remains to be identified. They express H+ -ATPase in the basolateral plasma membrane and in vesicles throughout the cytoplasm. A third type of intercalated cell with apical H+ -ATPase, but no AE1, has been described in the CNT and CCD of both rat and mouse. The prevalence of the third cell type is not known. The aim of this study was to characterize and quantify intercalated cell subtypes, including the newly described third non A-non B cell, in the CNT, ICT, and CCD of the rat and mouse. A triple immunolabeling procedure was developed in which antibodies to H+ -ATPase and band 3 protein were used to identify subpopulations of intercalated cells, and segment-specific antibodies were used to identify distal tubule and collecting duct segments. In both rat and mouse, intercalated cells constituted approximately 40% of the cells in the CNT, ICT, and CCD. Type A, type B, and non A-non B intercalated cells were observed in all of the three segments, with type A cells being the most prevalent in both species. In the mouse, however, non A-non B cells constituted more than half of the intercalated cells in the CNT, 39% in the ICT, and 22% in the CCD, compared with 14, 7, and 5%, respectively, in the rat. In contrast, type B intercalated cells accounted for only 8 to 16% of the intercalated cells in the three segments in the mouse compared with 26 to 39% in the rat. It is concluded that striking differences exist in the prevalence and distribution of the different types of intercalated cells in the CNT, ICT, and CCD of rat and mouse. In the rat, the non A-non B cells are fairly rare, whereas in the mouse, they constitute a major fraction of the intercalated cells, primarily at the expense of the type B intercalated cells.

Effect of acute respiratory acidosis on two populations of intercalated cells in rat cortical collecting duct

1987 ◽  
Vol 253 (6) ◽  
pp. F1142-F1156 ◽  
Author(s):  
J. W. Verlander ◽  
K. M. Madsen ◽  
C. C. Tisher
Keyword(s):  
Electron Microscopy ◽  
Collecting Duct ◽  
Respiratory Acidosis ◽  
Type A ◽  
Hydrogen Ion ◽  
Intercalated Cells ◽  
Cortical Collecting Duct ◽  
Type B ◽  
A Cells ◽  
Two Populations

Recent studies suggest the presence of two populations of intercalated cells in the rabbit cortical collecting duct (CCD), one involved with hydrogen ion secretion and another that may play a role in bicarbonate secretion. The purpose of this study was to determine whether two populations of intercalated cells are present in the rat CCD and to establish their response to acute respiratory acidosis. Rats were studied during normal acid-base conditions and after 4-5 h of respiratory acidosis. In all animals light microscopy and transmission and scanning electron microscopy revealed two configurations of intercalated cells, type A with an extensive apical tubulovesicular membrane compartment and prominent surface microprojections and type B with a well-developed vesicular compartment and short sparse surface microprojections. By transmission electron microscopy, studs were present on the cytoplasmic face of the apical plasmalemma and tubulovesicular profiles of A cells. In respiratory acidosis there was a striking increase in apical microprojections and in the surface density of the apical membrane of type A cells similar to the response observed previously in intercalated cells in the outer medullary collecting duct (OMCD) studied under the same physiological conditions. No changes were observed in type B cells. Scanning electron microscopy revealed no change in the relative number of type A and type B cells in respiratory acidosis. We conclude that two distinct populations of intercalated cells exist in the rat CCD: type A, which resembles the intercalated cells in the OMCD, and type B. The response of type A cells to acute respiratory acidosis and the similarity between these cells and intercalated cells in the OMCD, which are believed to secrete hydrogen ion, suggest that the type A cells are involved in hydrogen ion secretion in the CCD.

Immunohistochemical localization of H-K-ATPase α2c-subunit in rabbit kidney

2001 ◽  
Vol 281 (2) ◽  
pp. F357-F365 ◽  
Author(s):  
Jill W. Verlander ◽  
Robin M. Moudy ◽  
W. Grady Campbell ◽  
Brian D. Cain ◽  
Charles S. Wingo
Keyword(s):  
Collecting Duct ◽  
Type A ◽  
Immunohistochemical Localization ◽  
Macula Densa ◽  
Rabbit Kidney ◽  
Thick Ascending Limb ◽  
Intercalated Cells ◽  
Type B ◽  
Principal Cells ◽  
Medullary Collecting Duct

The rabbit kidney possesses mRNA for the H-K-ATPase α1-subunit (HKα1) and two splice variants of the H-K-ATPase α2-subunit (HKα2). The purpose of this study was to determine the specific distribution of one of these, the H-K-ATPase α2c-subunit isoform (HKα2c), in rabbit kidney by immunohistochemistry. Chicken polyclonal antibodies against a peptide based on the NH2 terminus of HKα2c were used to detect HKα2cimmunoreactivity in tissue sections. Immunohistochemical localization of HKα2c revealed intense apical immunoreactivity in a subpopulation of cells in the connecting segment, cortical collecting duct, and outer medullary collecting duct in both the outer and inner stripe. An additional population of cells exhibited a thin apical band of immunolabel. Immunohistochemical colocalization of HKα2c with carbonic anhydrase II, the Cl−/HCO[Formula: see text] exchanger AE1, and HKα1 indicated that both type A and type B intercalated cells possessed intense apical HKα2c immunoreactivity, whereas principal cells and connecting segment cells had only a thin apical band of HKα2c. Labeled cells were evident through the middle third of the inner medullary collecting duct in the majority of animals. Immunolabel was also present in papillary surface epithelial cells, cells in the cortical thick ascending limb of Henle's loop (cTAL), and the macula densa. Thus in the rabbit kidney, apical HKα2c is present and may contribute to acid secretion or potassium uptake throughout the connecting segment and collecting duct in both type A and type B intercalated cells, principal cells, and connecting segment cells, as well as in cells in papillary surface epithelium, cTAL, and macula densa.

Evaluation of cellular plasticity in the collecting duct during recovery from lithium-induced nephrogenic diabetes insipidus

2013 ◽  
Vol 305 (6) ◽  
pp. F919-F929 ◽  
Author(s):  
Francesco Trepiccione ◽  
Giovambattista Capasso ◽  
Søren Nielsen ◽  
Birgitte Mønster Christensen
Keyword(s):  
Time Course ◽  
Morphological Changes ◽  
Collecting Duct ◽  
Lithium Treatment ◽  
Transition Element ◽  
Type A ◽  
Functional Markers ◽  
Intercalated Cells ◽  
Anion Exchanger 1 ◽  
Principal Cells

The cellular morphology of the collecting duct is altered by chronic lithium treatment. We have previously shown that lithium increases the fraction of type-A intercalated cells and lowers the fraction of principal cells along the collecting duct. Moreover, type-A intercalated cells acquire a long-row distribution pattern along the tubules. In the present study, we show that these morphological changes reverse progressively after discontinuation of lithium and finally disappear after 19 days from lithium suspension. In this time frame we have identified for the first time, in vivo, a novel cellular type positive for both intercalated and principal cells functional markers, as recognized by colabeling with H+-ATPase/aquaporin-4 (AQP4) and anion exchanger-1 (AE-1)/AQP2 and Foxi1/AQP4. This cell type is mainly present after 6 days of lithium washout, and it disappears in parallel with the long-row pattern of the type-A intercalated cells. It usually localizes either in the middle or at the edge of the long-row pattern. Its ultrastructure resembles the intercalated cells as shown both by differential interference contrast and by electron microscopy. The time course of appearance, the localization along the collecting duct, and the ultrastructure suggest that the cells double labeled for principal and intercalated cells markers could represent a transition element driving the conversion of intercalated cells into principal cells.

Regulation of AE2 mRNA expression in the cortical collecting duct by acid/base balance

1998 ◽  
Vol 274 (3) ◽  
pp. F596-F601 ◽  
Author(s):  
Géza Fejes-Tóth ◽  
Erzsébet Rusvai ◽  
Emily S. Cleaveland ◽  
Anikó Náray-Fejes-Tóth
Keyword(s):  
Mrna Expression ◽  
Collecting Duct ◽  
Cell Types ◽  
Alkaline Media ◽  
Mrna Levels ◽  
Intercalated Cells ◽  
Cortical Collecting Duct ◽  
Acid Base Balance ◽  
Acid Base ◽  
Base Balance

AE2 mRNA and protein is expressed in several nephron segments, one of which is the cortical collecting duct (CCD). However, the distribution of AE2 among the different cell types of the CCD and the function of AE2 in the kidney are not known. The purpose of this study was to determine the distribution of AE2 mRNA among the three CCD cell types and to examine the effects of changes in acid/base balance on its expression. Following NH4Cl (acid) or NaHCO3 (base) loading of rabbits for ∼18 h, CCD cells were isolated by immunodissection. AE2 mRNA levels were determined by RT-PCR and were normalized for β-actin levels. We found that CCD cells express high levels of AE2 mRNA (∼500 copies/cell). AE2 mRNA levels were significantly higher in CCD cells originating from base-loaded than acid-loaded rabbits, with an average increase of 3.7 ± 1.07-fold. The effect of pH on AE2 mRNA levels was also tested directly using primary cultures of CCD cells. CCD cells incubated in acidic media expressed significantly lower levels of AE2 mRNA than those in normal or alkaline media. Experiments with isolated principal cells, α-intercalated cells, and β-intercalated cells (separated by fluorescence-activated cell sorting) demonstrated that AE2 mRNA levels are comparable in the three collecting duct cell subtypes and are similarly regulated by changes in acid/base balance. Based on these results, we conclude that adaptation to changes in extracellular H+ concentration is accompanied by opposite changes in AE2 mRNA expression. The observations that AE2 mRNA is not expressed in a cell-type-specific manner and that changes in acid/base balance have similar effects on each CCD cell subtype suggest that AE2 might serve a housekeeping function rather than being the apical anion exchanger of β-intercalated cells.

Axial heterogeneity of rabbit cortical collecting duct

1991 ◽  
Vol 260 (4) ◽  
pp. F498-F505
Author(s):  
C. L. Emmons ◽  
K. Matsuzaki ◽  
J. B. Stokes ◽  
V. L. Schuster
Keyword(s):  
Cross Sections ◽  
Cell Function ◽  
Rate Coefficient ◽  
Collecting Duct ◽  
Lectin Binding ◽  
Cell Types ◽  
Intercalated Cells ◽  
Cortical Collecting Duct ◽  
Principal Cells ◽  
Inner Cortex

The rabbit cortical collecting duct (CCD) consists of three major cell types: principal cells transport K+, beta-intercalated cells absorb Cl-, and alpha-intercalated cells secrete H+. We used functional and histological methods to assess axial distribution of these cell types along rabbit CCD. In perfused CCDs, lumen-to-bath Rb+ rate coefficient (an index of principal cell K+ transport) was not different in tubules from outer cortex (1 mm from renal surface) compared with those from inner cortex (2 mm from renal surface), suggesting that principal cell function is homogeneous along the CCD. In contrast, Cl- rate coefficient (a measure of beta-intercalated cell function) was twice as high in CCDs from outer compared with inner cortex, suggesting heterogeneity of beta-intercalated cells along the CCD. To further investigate these regional differences, we fixed and embedded kidneys and identified three cell types in CCD cross sections using carbonic anhydrase staining and peanut lectin binding. Comparing tubule cross sections from outer with those from inner cortex, we found no axial difference in the fraction of cells that were either principal cells (64%) or total (lectin binding and nonlectin binding) intercalated cells (36%). However, the lectin-binding intercalated cell subset was significantly increased in outer compared with inner cortex. We conclude that there is not heterogeneity of principal cells along the rabbit CCD; however, beta-cell number and function are increased in outer CCD. Collecting duct heterogeneity begins within the cortical segment.

Depletion of intercalated cells from collecting ducts of carbonic anhydrase II-deficient (CAR2 null) mice

1995 ◽  
Vol 269 (6) ◽  
pp. F761-F774 ◽  
Author(s):  
S. Breton ◽  
S. L. Alper ◽  
S. L. Gluck ◽  
W. S. Sly ◽  
J. E. Barker ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Collecting Duct ◽  
Water Channel ◽  
Immunofluorescent Staining ◽  
Specific Marker ◽  
Intercalated Cells ◽  
Cortical Collecting Duct ◽  
Principal Cells ◽  
Collecting Tubules ◽  
Deficient Mice

The kidneys of mice (CAR2-null mice) that are genetically devoid of carbonic anhydrase type II (CAII) were screened by immunocytochemistry with antibodies that distinguish intercalated and principal cells. Immunofluorescent localization of the anion exchanger AE1 and of the 56-kDa subunit of the vacuolar H(+)-adenosinetriphosphatase (H(+)-ATPase) was used to identify intercalated cells, while the AQP2 water channel was used as a specific marker for principal cells of the collecting duct. The CAII deficiency of the CAR2-null mice was first confirmed by the absence of immunofluorescent staining of kidney sections exposed to an anti-CAII antibody. Cells positive for AE1 and H(+)-ATPase were common in all collecting duct regions in normal mice but were virtually absent from the inner stripe of the outer medulla and the inner medulla of CAR2-null mice. The number of positive cells was also reduced threefold in the cortical collecting duct of CAR2-null animals compared with normal mice. In parallel, the percentage of AQP2-positive cells was correspondingly increased in the collecting tubules of CAII-deficient mice, whereas the total number of cells per tubule remained unchanged. These results suggest that intercalated cells are severely depleted and are replaced by principal cells in CAII-deficient mice. Quantitative analysis and double staining showed that, in the cortex, both type A and type B intercalated cells are equally affected. Elucidation of the mechanism(s) responsible for this phenotype will be of importance in understanding the origin and development of intercalated cells in the kidney.

Cellular actions of cAMP on HCO3(-)-secreting cells of rabbit CCD: dependence on in vivo acid-base status

1994 ◽  
Vol 266 (4) ◽  
pp. F528-F535 ◽  
Author(s):  
C. Emmons ◽  
J. B. Stokes
Keyword(s):  
Anion Exchanger ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Disulfonic Acid ◽  
Intercalated Cells ◽  
Cortical Collecting Duct ◽  
Acid Base ◽  
Acid Base Status

HCO3- secretion by cortical collecting duct (CCD) occurs via beta-intercalated cells. In vitro CCD HCO3- secretion is modulated by both the in vivo acid-base status of the animal and by adenosine 3',5'-cyclic monophosphate (cAMP). To investigate the mechanism of cAMP-induced HCO3- secretion, we measured intracellular pH (pHi) of individual beta-intercalated cells of CCDs dissected from alkali-loaded rabbits perfused in vitro. beta-Intercalated cells were identified by demonstrating the presence of an apical anion exchanger (cell alkalinization in response to removal of lumen Cl-). After 180 min of perfusion to permit decrease of endogenous cAMP, acute addition of 0.1 mM 8-bromo-cAMP or 1 microM isoproterenol to the bath caused a transient cellular alkalinization (> 0.20 pH units). In the symmetrical absence of either Na+, HCO3-, or Cl-, cAMP produced no change in pHi. Basolateral dihydrogen 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (0.1 mM) for 15 min before cAMP addition also prevented this alkalinization. In contrast to the response of cells from alkali-loaded rabbits, addition of basolateral cAMP to CCDs dissected from normal rabbits resulted in an acidification of beta-intercalated cells (approximately 0.20 pH units). The present studies demonstrate the importance of the in vivo acid-base status of the animal in the regulation of CCD HCO3- secretion by beta-intercalated cells. The results identify the possible existence of a previously unrecognized Na(+)-dependent Cl-/HCO3- exchanger on the basolateral membrane of beta-intercalated cells in alkali-loaded rabbits.

H(+)-K(+)-ATPase activity in rat collecting duct segments

1992 ◽  
Vol 262 (4) ◽  
pp. F692-F695 ◽  
Author(s):  
J. D. Gifford ◽  
L. Rome ◽  
J. H. Galla
Keyword(s):  
Atpase Activity ◽  
Marked Decrease ◽  
Collecting Duct ◽  
Intercalated Cells ◽  
Cortical Collecting Duct ◽  
Acid Base ◽  
Medullary Collecting Duct ◽  
Gastric Proton Pump

Previous studies have suggested the presence of an H(+)-K(+)-ATPase in rat cortical and medullary intercalated cells with similar properties to the gastric proton pump. The purpose of this study was to determine the functional contribution of an H(+)-K(+)-adenosinetriphosphatase(ATPase) to total CO2 (tCO2) transport along the rat collecting duct. After baseline determination of tCO2 transport in isolated perfused collecting duct segments, Sch 28080 (10 microM) was added to either the perfusate or bath. When Sch 28080 was added to the perfusate, there was no effect in the cortical collecting duct (CCD, 20.8 +/- 6.7 vs. 25.3 + 3.0 pmol.mm-1.min-1), but a marked decrease in tCO2 absorption was effected in both the outer medullary (OMCD, 37.6 + 6.2 vs. 10.7 +/- 4.1 pmol.mm-1.min-1) and initial inner medullary collecting duct (IMCD1, 34.4 +/- 8.1 vs. 16.2 +/- 5.6 pmol.mm-1.min-1). In the CCD from rats with acute alkalosis in vivo, Sch 28080 added to the bath inhibited tCO2 secretion in the CCD (-17.1 +/- 4.4 vs 3.5 + 3.3 pmol.mm-1.min-1). These findings suggest that 1) H(+)-K(+)-ATPase is important in tCO2 absorption in the OMCD and IMCD1 and in tCO2 secretion in the CCD, 2) HCO3(-)-absorbing intercalated cells differ functionally in the cortex and medulla, 3) HCO3- secretion is not the reverse process of HCO3- absorption in the CCD, and 4) H(+)-K(+)-ATPase is important in distal acidification under normal and altered acid-base conditions.

Cellular origin and hormonal regulation of K+-ATPase activities sensitive to Sch-28080 in rat collecting duct

2000 ◽  
Vol 279 (6) ◽  
pp. F1053-F1059 ◽  
Author(s):  
Nicolas Laroche-Joubert ◽  
Sophie Marsy ◽  
Alain Doucet
Keyword(s):  
Hormonal Regulation ◽  
Collecting Duct ◽  
Type I ◽  
Intercalated Cells ◽  
Cortical Collecting Duct ◽  
Type Iii ◽  
Principal Cells ◽  
Cellular Origin ◽  
Hormone Effects ◽  
A Cell

Rat collecting ducts exhibit type I or type III K+-ATPase activities when animals are fed a normal (NK) or a K+-depleted diet (LK). This study aimed at determining functionally the cell origin of these two K+-ATPases. For this purpose, we searched for an effect on K+-ATPases of hormones that trigger cAMP production in a cell-specific fashion. The effects of 1-deamino-8-d-arginine vasopressin (dD-AVP), calcitonin, and isoproterenol in principal cells, α-intercalated cells, and β-intercalated cells of cortical collecting duct (CCD), respectively, and of dD-AVP and glucagon in principal and α-intercalated cells of outer medullary collecting duct (OMCD), respectively, were examined. In CCDs, K+-ATPase was stimulated by calcitonin and isoproterenol in NK rats (type I K+-ATPase) and by dD-AVP in LK rats (type III K+-ATPase). In OMCDs, dD-AVP and glucagon stimulated type III but not type I K+-ATPase. These hormone effects were mimicked by the cAMP-permeant analog dibutyryl-cAMP. In conclusion, in NK rats, cAMP stimulates type I K+-ATPase activity in α- and β-intercalated CCD cells, whereas in LK rats it stimulates type III K+-ATPase in principal cells of both CCD and OMCD and in OMCD intercalated cells.

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