Mechanism of apical and basolateral Na(+)-independent Cl-/base exchange in the rabbit superficial proximal straight tubule.

Kurtz, Ira; Nagami, Glenn T.; Yanagawa, Norimoto; Li, L; Emmons, C; Lee, I

doi:10.1172/jci117304

Cited by 41 publications

(35 citation statements)

References 55 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Measurements of intracellular pH have indicated that Cl Ϫ -HCO 3 Ϫ exchange activity is present on the apical membrane of proximal tubule cells (16,27), although there is nephron heterogeneity in this regard (16). The present and previous (12) findings suggest that Slc26a6 may account for this transport activity.…”

Section: Discussionmentioning

confidence: 45%

Specificity of Anion Exchange Mediated by Mouse Slc26a6

Jiang

Grichtchenko

Boron

et al. 2002

Journal of Biological Chemistry

143

149

View full text Add to dashboard Cite

Recently, CFEX, the mouse orthologue of human SLC26A6, was localized to the brush border membrane of proximal tubule cells and was demonstrated to mediate Cl ؊ -formate exchange when expressed in Xenopus oocytes. The purpose of the present study was to examine whether mouse Slc26a6 can mediate one or more of the additional anion exchange processes observed to take place across the apical membrane of proximal tubule cells. The majority of Na ϩ , Cl Ϫ , and HCO 3 Ϫ filtered by the kidney is reabsorbed in the proximal tubule. Studies using isolated brush border vesicles and perfused tubules are consistent with the concept that a major fraction of Cl Ϫ entry across the apical membrane of proximal tubule cells occurs via Cl Ϫ -formate exchange and Cl Ϫ -oxalate exchange (1). The molecular identification of the transporter(s) responsible for these anion exchange activities has yet to be established with certainty. Recently, CFEX, the mouse orthologue of human SLC26A6 (2, 3), was demonstrated to be capable of mediating Cl Ϫ -formate exchange when expressed in Xenopus oocytes, and it was localized to the brush border membrane of proximal tubule cells by immunocytochemistry (4). Thus, Slc26a6 was proposed as a candidate to mediate Cl Ϫ -formate exchange in the proximal tubule (4).The purpose of the present study was to characterize the anion specificity of Slc26a6 in more detail and to test specifically the ability of Slc26a6 to mediate additional anion exchange processes known to take place across the apical membrane of proximal tubule cells, such as Cl Ϫ -oxalate exchange. We find that mouse Slc26a6 can mediate transport of oxalate, sulfate, and HCO 3 Ϫ in addition to Cl Ϫ and formate and can function in multiple exchange modes involving pairs of these anions, including Cl Ϫ -oxalate exchange. MATERIALS AND METHODS Measurements of Radiolabeled SoluteFluxes-Mouse Slc26a6 (CFEX) cDNA was subcloned into the Xenopus expression plasmid pGH19 (5) and heterologously expressed in Xenopus oocytes as described previously (4). For the experiments in this study, oocytes were injected with 50 nl of water (control) or Slc26a6 cRNA (25 ng), and transport was assayed 2 days later. For measurements of solute influx, oocytes were washed twice in 1 ml chloride-free buffer (98 mM potassium-gluconate/1.8 mM hemi-calcium-gluconate/1 mM hemi-magnesiumgluconate/5 mM Tris-Hepes, pH 7.5) and then incubated in 500 l of uptake solution (100 mM potassium-gluconate/5 mM Tris, pH adjusted to 7.5 with Hepes) containing the radiolabeled solutes to be tested ( 1 After 30-min incubation at room temperature, external isotope was removed by washing the oocytes three times with 1 ml of ice-cold chloride-free buffer. For efflux measurements, oocytes were first preloaded with radioisotope by incubating for 60 min in chloride-free buffer containing [ 14 C]oxalate. After three washes in ice-cold chloride-free buffer, the radioisotope content of oocytes was measured both initially and 15 min after suspension in solution containing test anions. Net efflux was ca...

show abstract

Section: Discussionmentioning

confidence: 45%

Specificity of Anion Exchange Mediated by Mouse Slc26a6

Jiang

Grichtchenko

Boron

et al. 2002

Journal of Biological Chemistry

143

149

View full text Add to dashboard Cite

show abstract

“…For example, studies examining the apical Cl Ϫ /base exchanger by cell pH measurement have been less successful in demonstrating the stimulation of this transporter by formate. Two studies in microperfused kidney proximal tubule have not been consistent in detecting stimulation of apical Cl Ϫ /base exchange by formate (7,20). These results have raised serious questions in regard to the role of apical Cl Ϫ /formate exchange as the mediator of enhanced Na ϩ and Cl Ϫ reabsorption in the proximal tubule by formate (45).…”

Section: Discussionmentioning

confidence: 99%

“…The resultant formic acid diffuses back which, in turn, can provide the proximal tubule cell with a Cl Ϫ /base exchange mechanism that, in essence, is driven by recycling of formate across the luminal membrane (15,16). Studies evaluating this issue in the kidney proximal tubule, however, found that luminal membrane formic acid permeability is too low to support this mechanism (20,27). An alternative mechanism has been proposed which suggests that formate is recycled back by exchanging with cellular OH Ϫ (5).…”

Section: /Hmentioning

confidence: 99%

“…Intrinsic cell buffer capacity (␤ i) was measured by using NH4Cl prepulse technique according to the established protocols as previously described (20,24,29,34,35). Measurement of ␤ i was done in solutions without sodium (solution 4, Table 1) with 1 mM DIDS on both bath and luminal side to keep sodium-and chloride-dependent acidification mechanisms inactive.…”

Section: In the Experiments In Which CLmentioning

confidence: 99%

“…In the experiments in which the effect of formate was tested, 0.5 mM K ϩ -formate was added to solutions 2, 3, 4, or 5. (20,29). The buffer capacity in the presence of bicarbonate was 70.22 Ϯ 8 mM (n ϭ 7 cells in 2 tubules).…”

Section: In the Experiments In Which CLmentioning

confidence: 99%

See 2 more Smart Citations

Activation of the apical Na⁺/H⁺exchanger NHE3 by formate: a basis of enhanced fluid and electrolyte reabsorption by formate in the kidney

Petrovic

Barone²,

Weinstein³

et al. 2004

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Formate stimulates sodium chloride and fluid reabsorption in kidney proximal tubule; however, the exact cellular mechanism of this effect remains unknown. We hypothesized that the primary target of formate is the apical Na+/H+ exchanger. Here, we demonstrate that formate directly enhances the apical Na+/H+ exchanger (NHE3) activity in mouse kidney proximal tubule. In the absence of CO2/HCO3−, addition of formate (500 μM) to the bath and lumen of microperfused mouse kidney proximal tubule caused significant intracellular alkalinization, with intracellular pH (pHi) increasing from baseline levels 7.17 ± 0.01 to 7.55 ± 0.01 ( P < 0.001, n = 14), with a ΔpH of 0.38 ± 0.02. Removal of luminal chloride did not block cell pH alkalinization by formate (baseline pH of 7.26 ± 0.01 to 7.53 ± 0.01 with formate, P < 0.001, n = 10), indicating that the apical Cl−/OH− exchanger was not the primary mediator of the effect of formate on cell pH. However, removal of sodium from the lumen or addition of EIPA completely prevented cell pH alkalinization. Addition of formate to the lumen and bath in the outer medullary collecting duct, which does not express any apical Na+/H+ exchanger, did not cause any cell pH alkalinization. At lower concentrations (50 μM), formate caused significant pHi alkalinization in proximal tubule cells, with pHi increasing from baseline levels 7.15 ± 0.02 to 7.36 ± 0.02 ( P < 0.02, n = 11). Acetate, at 50 μM, had no effect on pHi. Formate’s effect was observed both in the absence and presence of CO2/HCO3− in the media. We conclude that formate stimulates the apical Na+/H+ exchanger NHE3 in the kidney proximal tubule. We propose that formate stimulation of chloride reabsorption in the proximal tubule is indirect and is secondary to the activation of apical Na+/H+ exchanger NHE3, which then leads to the stimulation of the apical chloride/base exchanger.

show abstract

Chloride Transport

Edwards

2012

Comprehensive Physiology

View full text Add to dashboard Cite

Chloride transport along the nephron is one of the key actions of the kidney that regulates extracellular volume and blood pressure. To maintain steady state, the kidney needs to reabsorb the vast majority of the filtered load of chloride. This is accomplished by the integrated function of sequential chloride transport activities along the nephron. The detailed mechanisms of transport in each segment generate unique patterns of interactions between chloride and numerous other individual components that are transported by the kidney. Consequently, chloride transport is inextricably intertwined with that of sodium, potassium, protons, calcium, and water. These interactions not only allow for exquisitely precise regulation but also determine the particular patterns in which the system can fail in disease states. © 2012 American Physiological Society. Compr Physiol 2:1061‐1092, 2012.

show abstract

Mechanism of apical and basolateral Na(+)-independent Cl-/base exchange in the rabbit superficial proximal straight tubule.

Cited by 41 publications

References 55 publications

Specificity of Anion Exchange Mediated by Mouse Slc26a6

Specificity of Anion Exchange Mediated by Mouse Slc26a6

Activation of the apical Na⁺/H⁺exchanger NHE3 by formate: a basis of enhanced fluid and electrolyte reabsorption by formate in the kidney

Chloride Transport

Contact Info

Product

Resources

About

Mechanism of apical and basolateral Na(+)-independent Cl-/base exchange in the rabbit superficial proximal straight tubule.

Cited by 41 publications

References 55 publications

Specificity of Anion Exchange Mediated by Mouse Slc26a6

Specificity of Anion Exchange Mediated by Mouse Slc26a6

Activation of the apical Na+/H+exchanger NHE3 by formate: a basis of enhanced fluid and electrolyte reabsorption by formate in the kidney

Chloride Transport

Contact Info

Product

Resources

About

Activation of the apical Na⁺/H⁺exchanger NHE3 by formate: a basis of enhanced fluid and electrolyte reabsorption by formate in the kidney