Chloride transport by the cortical and outer medullary collecting duct

1987 ◽  
Vol 253 (2) ◽  
pp. F203-F212 ◽  
Author(s):  
V. L. Schuster ◽  
J. B. Stokes
Keyword(s):  
Chloride Transport ◽  
Collecting Duct ◽  
Exchange Process ◽  
Basolateral Membrane ◽  
Fine Tuning ◽  
Transport Systems ◽  
Acid Base ◽  
Intercalated Cell ◽  
Cl Channel ◽  
Collecting Tubule

The processes by which chloride is transported by the cortical and outer medullary collecting tubule have been most extensively studied using in vitro microperfusion of rabbit tubules. Chloride appears to be transported by three major mechanisms. First, Cl can be actively reabsorbed by an electroneutral Cl-HCO3 exchanger localized to the apical membrane of the HCO3-secreting (beta-type) intercalated cell. Cl exits this cell via a basolateral Cl channel. This anion exchange process can also operate in a Cl self-exchange mode, is stimulated acutely by beta-adrenergic agonists and cAMP, and is regulated chronically by in vivo acid-base status. Second, Cl can diffuse passively down electrochemical gradients via the paracellular pathway. Although this pathway does not appear to be selectively permeable to Cl, it is large enough to allow for significant passive reabsorption. Third, Cl undergoes recycling across the basolateral membrane of the H+-secreting (alpha-type) intercalated cell. HCO3 exit from this cell brings Cl into the cell via electroneutral Cl-HCO3 exchange; Cl then exits the cell via a Cl channel. Cl transport is thus required for acidification and alkalinization of the urine. Both of these processes exist in the cortical collecting tubule. Their simultaneous operation allows fine tuning of acid-base excretion. In addition, these transport systems, when functioning at equal rates, effect apparent electrogenic net Cl absorption without changing net HCO3 transport. These systems may play an important role in regulating Cl balance.

Phenotypic plasticity in the intercalated cell: the hensin pathway

1998 ◽  
Vol 275 (2) ◽  
pp. F183-F190 ◽  
Author(s):  
Qais Al-Awqati ◽  
S. Vijayakumar ◽  
C. Hikita ◽  
J. Chen ◽  
J. Takito
Keyword(s):  
Collecting Duct ◽  
Basolateral Membrane ◽  
Cell Types ◽  
Band 3 ◽  
Cytoskeletal Proteins ◽  
Β Cell ◽  
Biochemical Basis ◽  
Intercalated Cell ◽  
Immortalized Cell

The collecting duct of the renal tubule contains two cell types, one of which, the intercalated cell, is responsible for acidification and alkalinization of urine. These cells exist in a multiplicity of morphological forms, with two extreme types, α and β. The former acidifies the urine by an apical proton-translocating ATPase and a basolateral Cl/HCO3 exchanger, which is an alternately spliced form of band 3. This kidney form of band 3, kAE1, is present in the apical membrane of the β-cell, which has the H+-ATPase on the basolateral membrane. We had suggested previously that metabolic acidosis leads to conversion of β-types to α-types. To study the biochemical basis of this plasticity, we used an immortalized cell line of the β-cell and showed that these cells convert to the α-phenotype when plated at superconfluent density. At high density these cells localize a new protein, which we term “hensin,” to the extracellular matrix, and hensin acts as a molecular switch capable of changing the phenotype of these cells in vitro. Hensin induces new cytoskeletal proteins, makes the cells assume a more columnar shape and retargets kAE1 and the H+-ATPase. These recent studies suggest that the conversion of β- to α-cells, at least in vitro, bears many of the hallmarks of terminal differentiation.

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.

Interaction of Cl- and other halogens with Cl- transport systems in rabbit cortical collecting duct

1992 ◽  
Vol 263 (5) ◽  
pp. F870-F877 ◽  
Author(s):  
S. Muto ◽  
M. Imai ◽  
Y. Asano
Keyword(s):  
Apical Membrane ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Cell Types ◽  
Transport Systems ◽  
Cortical Collecting Duct ◽  
Cl Transport ◽  
Distinct Cell ◽  
Cl Conductance ◽  
Basolateral Membrane Potential

We have reported that in the rabbit cortical collecting duct (CCD) we can identify electrophysiologically three distinct cell types; the collecting duct (CD) cell and the alpha- and beta-intercalated (IC) cell. To further characterize the Cl- transport properties of each cell type, we examined the interaction between Cl- and other halogens or SCN- in the isolated and perfused CCD by intracellular microelectrode impalement. The rapid depolarization of the basolateral membrane potential (VB) caused by replacement of bath Cl- with each anion revealed that the sequences of apparent halogen selectivity for the basolateral Cl- conductance were similar in all three cell types. The ranking of Cl- > Br- > F- > I- corresponds to the sequence 5 of Eisenman's series, indicating “strong” interaction of the anions with the selectivity site. The basolateral Cl- conductance of these three cell types may share common characteristics, although I- permeability is less in IC cells than in CD cells. Hyperpolarization of the basolateral membrane of the beta-IC cell upon reduction of luminal Cl- reflects alterations in either Cl- entry across the apical membrane, or Cl- exit across the basolateral membrane, or both. Luminal Cl- replacement with each anion showed that the sequence of the hyperpolarization of the basolateral membrane was I- >> cyclamate = SCN- > F- > Br-, suggesting that I-inhibits either apical Cl- entry or basolateral Cl- exit. On the other hand, in the CD cell reduction of the perfusate Cl- by replacement with each anion caused the basolateral membrane to hyperpolarize with a different ranking: cyclamate = F- > I- = SCN- > Br-.(ABSTRACT TRUNCATED AT 250 WORDS)

AE4 is a DIDS-sensitive Cl−/HCO 3 − exchanger in the basolateral membrane of the renal CCD and the SMG duct

2002 ◽  
Vol 283 (4) ◽  
pp. C1206-C1218 ◽  
Author(s):  
Shigeru B. H. Ko ◽  
Xiang Luo ◽  
Henrik Hager ◽  
Alexandra Rojek ◽  
Joo Young Choi ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Basolateral Membrane ◽  
Rabbit Kidney ◽  
Intercalated Cells ◽  
Cortical Collecting Duct ◽  
Acid Base ◽  
Specific Expression ◽  
Hek 293 ◽  
Acid Base Status ◽  
Species Specific

The renal cortical collecting duct (CCD) plays an important role in systemic acid-base homeostasis. The β-intercalated cells secrete most of the HCO[Formula: see text], which is mediated by a luminal, DIDS-insensitive, Cl−/HCO[Formula: see text] exchange. The identity of the luminal exchanger is a matter of debate. Anion exchanger isoform 4 (AE4) cloned from the rabbit kidney was proposed to perform this function (Tsuganezawa H et al. J Biol Chem 276: 8180–8189, 2001). By contrast, it was proposed (Royaux IE et al. Proc Natl Acad Sci USA 98: 4221–4226, 2001) that pendrin accomplishes this function in the mouse CCD. In the present work, we cloned, localized, and characterized the function of the rat AE4. Northern blot and RT-PCR showed high levels of AE4 mRNA in the CCD. Expression in HEK-293 and LLC-PK1 cells showed that AE4 is targeted to the plasma membrane. Measurement of intracellular pH (pHi) revealed that AE4 indeed functions as a Cl−/HCO[Formula: see text] exchanger. However, AE4 activity was inhibited by DIDS. Immunolocalization revealed species-specific expression of AE4. In the rat and mouse CCD and the mouse SMG duct AE4 was in the basolateral membrane. By contrast, in the rabbit, AE4 was in the luminal and lateral membranes. In both, the rat and rabbit CCD AE4 was in α-intercalated cells. Importantly, localization of AE4 was not affected by the systemic acid-base status of the rats. Therefore, we conclude that expression and possibly function of AE4 is species specific. In the rat and mouse AE4 functions as a Cl−/HCO[Formula: see text] exchanger in the basolateral membrane of α-intercalated cells and may participate in HCO[Formula: see text] absorption. In the rabbit AE4 may contribute to HCO[Formula: see text] secretion.

Expression of acid-base-related proteins in mesonephric kidney of the rabbit

1994 ◽  
Vol 267 (6) ◽  
pp. F987-F997 ◽  
Author(s):  
T. Matsumoto ◽  
C. A. Winkler ◽  
L. P. Brion ◽  
G. J. Schwartz
Keyword(s):  
Collecting Duct ◽  
Cell Types ◽  
Intercalated Cells ◽  
Acid Base ◽  
Principal Cells ◽  
Collecting Tubule ◽  
Metanephric Kidney ◽  
Collecting Tubules ◽  
Related Proteins ◽  
Different Cell Types

The mesonephric kidney, precursor to the metanephric kidney, comprises 30-50 nephrons, each with a glomerulus and proximal, distal, and collecting tubules. Although two different cell types have been identified in the mesonephric collecting tubule, no relationship to cells of the metanephric collecting duct has been established. To characterize expression of some of the acid-base-related proteins, we assayed for carbonic anhydrase (CA) activity and performed immunocytochemistry in mesonephroi from 15- to 20-day-old fetal rabbits. From total RNA, we detected expression of CA II and CA IV mRNA. Microdissected proximal and collecting tubules abundantly expressed both CA II and CA IV, at least to the extent observed in mature metanephric proximal tubules and collecting ducts. Histochemistry confirmed the expression of CA activity in these segments; in the collecting tubule, 28% of the collecting tubule cells were CA rich. Most CA-rich cells showed apical H(+)-ATPase and basolateral band 3 anion exchanger staining consistent with the findings in mature H(+)-secreting (alpha) intercalated cells of the metanephric collecting duct. CA-negative cells could be labeled with an antibody that identifies mature metanephric principal cells. Thus the mesonephric collecting tubule has many cells resembling mature alpha-intercalated cells and a majority of cells resembling principal cells. The similarity to the metanephric collecting duct suggests that the lineages of metanephric alpha-intercalated and principal cells may be closely related to those of the mesonephros.

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.

Double-barreled chloride channels of collecting duct basolateral membrane

1990 ◽  
Vol 259 (1) ◽  
pp. F46-F52 ◽  
Author(s):  
S. C. Sansom ◽  
B. Q. La ◽  
S. L. Carosi
Keyword(s):  
Chloride Channels ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Electric Organ ◽  
Cortical Collecting Duct ◽  
Cl Channel ◽  
Voltage Dependent ◽  
Cl Channels ◽  
Excised Patches ◽  
High Concentrations

Microelectrode studies have shown that the basolateral membrane of the principal cells (PC) of the rabbit cortical collecting duct (CCD) contains Cl(-)-conductive pathways. To determine the properties of single Cl- channels we prepared the basolateral membrane for patch clamping by incubating the CCD in collagenase and/or tearing the basement membrane with a fine needle. When high concentrations of collagenase were used, only a small nonselective channel was observed. In low concentrations or the absence of collagenase, however, we identified a Cl- channel (g46) in both cell-attached and excised patches. The Cl- channel gated rapidly between three equally spaced substates of 0 (S0), 23 (S1), and 46 pS (S2) and slowly between states C (inactive) and S0. The conductance of each substate was not voltage dependent between pipette potentials from -60 to +60 mV (cell attached). The probability that the channel gated from C to S0 increased with hyperpolarizing potentials, but the probability that g46 was in substate S0 increased with depolarizing patch potentials. This channel was similar to that described by Miller for the nonexcitable membrane of the electric organ of Torpedo californica. Because g46 was the most frequently observed basolateral membrane channel and was voltage dependent at physiological potentials, it is probably the channel responsible for the dominant Cl- conductance of PC.

scholarly journals Slc4a8 in the Kidney: Expression, Subcellular Localization and Role in Salt Reabsorption

2018 ◽  
Vol 50 (4) ◽  
pp. 1361-1375 ◽  
Author(s):  
Jie Xu ◽  
Sharon Barone ◽  
Kamyar Zahedi ◽  
Marybeth Brooks ◽  
Manoocher Soleimani
Keyword(s):  
In Situ Hybridization ◽  
Subcellular Localization ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Acid Base ◽  
Duct Cells ◽  
Collecting Ducts ◽  
Collecting Duct Cells ◽  
Medullary Collecting Duct

Background/Aims: The sodium-dependent bicarbonate transporter Slc4a8 (a.k.a NDCBE) mediates the co-transport of sodium and bicarbonate in exchange for chloride. It is abundantly detected in the brain, with low expression levels in the kidney. The cell distribution and subcellular localization of Slc4a8 in the kidney and its role in acid/base and electrolyte homeostasis has been the subject of conflicting reports. There are no conclusive localization or functional studies to pinpoint the location and demonstrate the function of Slc4a8 in the kidney. Methods: Molecular techniques, including RT-PCR and in situ hybridization, were performed on kidney sections and tagged epitopes were used to examine the membrane targeting of Slc4a8 in polarized kidney cells. Crispr/Cas9 was used to generate and examine Slc4a8 KO mice. Results: Zonal distribution and in situ hybridization studies showed very little expression for Slc4a8 (NDCBE) in the cortex or in cortical collecting ducts (CCD). Slc4a8 was predominantly detected in the outer and inner medullary collecting ducts (OMCD and IMCD), and was targeted to the basolateral membrane of osmotically tolerant MDCK cells. Slc4a8 KO mice did not show any abnormal salt or bicarbonate wasting under baseline conditions or in response to bicarbonate loading, salt restriction or furosemide-induced diuresis. Conclusion: Slc4a8 (NDCBE) is absent in the CCD and is predominantly localized on the basolateral membrane of medullary collecting duct cells. Further, Slc4a8 deletion does not cause significant acid base or electrolyte abnormalities in pathophysiologic states. Additional studies are needed to examine the role of Slc4a8 (NDCBE) in intracellular pH and volume regulation in medullary collecting duct cells.

Two types of collecting duct mitochondria-rich (intercalated) cells: lectin and band 3 cytochemistry

1986 ◽  
Vol 251 (3) ◽  
pp. C347-C355 ◽  
Author(s):  
V. L. Schuster ◽  
S. M. Bonsib ◽  
M. L. Jennings
Keyword(s):  
Anion Exchange ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Succinic Dehydrogenase ◽  
Band 3 ◽  
Rabbit Kidney ◽  
Intercalated Cells ◽  
Peanut Lectin ◽  
Collecting Tubule ◽  
Collecting Tubules

Anion exchange plays an important role in renal ion transport and acidification. To further understand the molecular nature of renal epithelial anion exchange, we used a monoclonal antibody to the membrane domain (52 kDa) of human erythrocyte band 3 protein to immunocytochemically search for this polypeptide in the rabbit kidney. In cryostat sections, a subpopulation of cells in the cortical and outer medullary collecting tubules showed immunoreactivity; labeling was restricted to the basolateral membrane. Proximal tubules and thick and thin limbs of Henle showed no immunoreactivity. Approximately 11% of cells in the cortical, but 43% of cells in the medullary, collecting tubule were positive for band 3. To determine the type of cells that were band 3 positive, mitochondria-rich (intercalated) cells were identified by their positive histochemical staining for succinic dehydrogenase activity and by their ability to bind peanut lectin at the apical membrane. In the cortical collecting tubule, the majority of mitochondria-rich cells bound peanut lectin but were band 3 negative; the remainder were band 3 positive but lectin negative. This distribution was reversed in the inner stripe of the outer medulla: all mitochondria-rich cells were band 3 positive and lectin negative. Thus mitochondria-rich cells are of at least two types, each of which has a distinct axial distribution pattern. Given available information about in vitro HCO3 transport properties of rabbit collecting tubules, it is likely that the lectin-positive, band 3-negative mitochondria-rich cells secrete HCO3, whereas the lectin-negative, band 3-positive cells reabsorb HCO3 (secrete H).

Sign in / Sign up

Export Citation Format

Share Document