Electroneutral K+/HCO3- cotransport in cells of medullary thick ascending limb of rat kidney.

Leviel, F.; Borensztein, Pascale; Houillier, Pascal; Paillard, Michel; Bichara, M.

doi:10.1172/jci115962

Cited by 46 publications

(20 citation statements)

References 27 publications

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“…These results do not confirm the absence of Cl Ϫ / HCO 3 Ϫ exchange described in rat MTALH suspensions (28). In contrast, they are in complete agreement with the results recently obtained in our laboratory using purified basolateral membrane vesicles from rat MTALH cells.…”

Section: Discussionsupporting

confidence: 49%

“…Values for dpHi /dt were determined by a computer-assisted fitting of the pHi vs. time data to a linear regression line over the first [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] In the presence of 0.15 mM bath DIDS and in the basolateral presence of Cl Ϫ , pH i was not stable but steadily increasing (segment a-b, Fig. 1B), at variance with data obtained in the absence of peritubular DIDS (Fig.…”

Section: Methodsmentioning

confidence: 86%

“…In the proximal tubule, the basolateral HCO 3 Ϫ exit relies on the parallel activity of distinct transporters (1,2), and it may be considered that the same may occur in other tubular segments. In addition, at least two other basolateral HCO 3 Ϫ transport mechanisms have been suggested to be present in the murine MTALH cell suspensions (23,28). Therefore, it was mandatory to assess whether any of these transporters is present in intact rat MTALH cells.…”

Section: Discussionmentioning

confidence: 99%

“…Previous experiments examining HCO 3 Ϫ exit mechanisms have been mainly conducted with MTALH suspensions. 4,4Ј-Diisothiocyanostilbene-2,2Ј-disulfonic acid (DIDS)-sensitive Na ϩ -(HCO 3 Ϫ ) n and Ba 2ϩ -insensitive electroneutral K ϩ -HCO 3 Ϫ cotransports have been described in mouse and rat MTALH suspensions, respectively, and no evidence for the presence of Cl Ϫ /HCO 3 Ϫ exchange has been found in mouse and rat MTALH suspensions (23,28). However, these data have recently been challenged by the results of a study using purified basolat-eral membrane vesicles from rat MTALH cells (29).…”

mentioning

confidence: 99%

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Basolateral membrane Cl⁻-, Na⁺-, and K⁺-coupled base transport mechanisms in rat MTALH

Massé

Paillard

Houillier

2002

American Journal of Physiology-Renal Physiology

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Mechanisms involved in basolateral HCO[Formula: see text] transport were examined in the in vitro microperfused rat medullary thick ascending limb of Henle (MTALH) by microfluorometric monitoring of cell pH. Removing peritubular Cl− induced a cellular alkalinization that was inhibited in the presence of peritubular 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) and blunted in the absence of external CO2/HCO[Formula: see text]. The alkalinization elicited by removing peritubular Cl−persisted in the bilateral absence of Na+, together with a voltage clamp. When studied in Cl−-free solutions, lowering peritubular pH induced a base efflux that was inhibited by peritubular DIDS or by the absence of external CO2/HCO[Formula: see text]. Removing peritubular Na+ elicited a cellular acidification that was accounted for by stimulation of a DIDS- and ethylisopropylamiloride (EIPA)-insensitive Na+-HCO[Formula: see text] cotransport and inhibition of a basolateral Na+/H+exchange. Increasing bath K+ induced an intracellular alkalinization that was inhibited in the absence of external CO2/HCO[Formula: see text]. At 2 mM, peritubular Ba2+, which inhibits the K+-Cl−cotransport, did not induce any change in transepithelial voltage but elicited a cellular alkalinization and inhibited K+-induced cellular alkalinization, consistent with the presence of a basolateral, electroneutral Ba2+-sensitive K+-Cl− cotransport that may operate as a K+-HCO[Formula: see text] cotransport. This cotransport was inhibited in the peritubular presence of furosemide, [(dihydroindenyl)oxy]alkanoic acid, 5-nitro-2-(3-phenylpropylamino)benzoate, or DIDS. At least three distinct basolateral HCO[Formula: see text] transport mechanisms are functional under physiological conditions: electroneutral Cl−/HCO[Formula: see text] exchange, DIDS- and EIPA-insensitive Na+-HCO[Formula: see text] cotransport, and Ba2+-sensitive electroneutral K+-Cl−(HCO[Formula: see text]) cotransport.

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Section: Discussionsupporting

confidence: 49%

Section: Methodsmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Basolateral membrane Cl⁻-, Na⁺-, and K⁺-coupled base transport mechanisms in rat MTALH

Massé

Paillard

Houillier

2002

American Journal of Physiology-Renal Physiology

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“…The method used to isolate MTAL fragments has been previously described in detail (17,18). Because we have previously shown that glucocorticoids regulate BSC1 expression (19), MTAL fragments were harvested from rats that were adrenalectomized (ADX) and given isotonic saline as drink-ing water 6 d before the experiments to avoid any interference caused by endogenous glucocorticoids.…”

Section: Freshly Isolated Mtal Tubulesmentioning

confidence: 99%

Acid pH Increases the Stability of BSC1/NKCC2 mRNA in the Medullary Thick Ascending Limb

Karim

Attmane-Elakeb

Sibella

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Chronic metabolic acidosis enhances the ability of the medullary thick ascending limb (MTAL) to absorb NH 4 ϩ at least in part by stimulating the mRNA and protein expression of BSC1/NKCC2, the MTAL apical Na ϩ -K ϩ (NH 4 ϩ )-2Cl Ϫ co-transporter. For assessing the mechanism by which an acid pH enhances the BSC1 mRNA abundance, MTAL were harvested from adrenalectomized rats and incubated in control (pH 7.35) and acid (pH 7.10) 1:1 mixtures of Ham's nutrient mixture F-12 and DME. rBSC1 mRNA abundance and gene transcription rate were quantified by quantitative reverse transcription-PCR and run-off assay, respectively. Acid incubation enhanced mRNA abundance within 4 h in whole cell (P Ͻ 0.02) but not in nucleus. BSC1 gene transcription rate was not affected by acid incubation. In contrast, under conditions in which gene transcription was blocked, rBSC1 mRNA decreased within 6 h by 38 Ϯ 11% in control but only by 15 Ϯ 15% in acid medium (P Ͻ 0.02), which represented an increase in the BSC1 mRNA half-life from approximately 7 to approximately 17 h. Furthermore, in a mouse TAL cell line, acid incubation for 16 h significantly increased (P Ͻ 0.02) the amount of BSC1 mRNA in cells transfected with the fulllength mBSC1 cDNA but not in cells transfected with a mBSC1 cDNA lacking the 3'-UTR. These results demonstrate that acid pH enhances the stability of BSC1 mRNA probably by activating pathways that act on the AU-rich 3'-UTR of BSC1 mRNA, which contributes to the renal response to metabolic acidosis. Increased urinary NH 4ϩ excretion, which augments acid excretion, has long been recognized to be quantitatively the major compensatory response of the kidney against chronic metabolic acidosis (CMA) (1). It is established that most of ammonia that leaves the proximal tubule is absorbed by the medullary thick ascending limb (MTAL), which causes ammonia accumulation in the medullary interstitium followed by its secretion in adjacent medullary collecting tubule (2). The role of MTAL ammonia absorption may be particularly important in states of CMA because micropuncture experiments have shown that the NH 4 ϩ amount absorbed by the loop of Henle is increased under the latter condition (3,4). In this regard, Good (5) has shown that rat MTAL isolated and perfused in vitro have an increased ability to absorb NH 4 ϩ in response to CMA. This adaptive response in MTAL would substantially augment NH 4 ϩ excretion during metabolic acidosis.It is established that the luminal step of MTAL NH 4 ϩ absorption largely involves the MTAL bumetanide-sensitive Na ϩ -K ϩ (NH 4 ϩ )-2Cl Ϫ apical co-transporter (6 -10) that was recently cloned in various species and named BSC1 or NKCC2 (11)(12)(13)(14)(15). We recently demonstrated that CMA upregulate BSC1 expression. Indeed, BSC1 mRNA abundance significantly increased 3 h after the creation of metabolic acidosis by peritoneal dialysis, which was followed within 24 h by an augmentation of the BSC1 protein abundance (16). The augmentation of both mRNA and protein abundance persisted after 6 d...

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Cation‐Coupled Bicarbonate Transporters

Aalkjær

Boedtkjer

Choi

et al. 2014

Comprehensive Physiology

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Cation-coupled HCO3− transport was initially identified in the mid-1970s when pioneering studies showed that acid extrusion from cells is stimulated by CO2/HCO3− and associated with Na+ and Cl− movement. The first Na+-coupled bicarbonate transporter (NCBT) was expression-cloned in the late 1990s. There are currently five mammalian NCBTs in the SLC4-family: the electrogenic Na,HCO3-cotransporters NBCe1 and NBCe2 (SLC4A4 and SLC4A5 gene products); the electroneutral Na,HCO3-cotransporter NBCn1 (SLC4A7 gene product); the Na+-driven Cl,HCO3-exchanger NDCBE (SLC4A8 gene product); and NBCn2/NCBE (SLC4A10 gene product), which has been characterized as an electroneutral Na,HCO3-cotransporter or a Na+-driven Cl,HCO3-exchanger. Despite the similarity in amino acid sequence and predicted structure among the NCBTs of the SLC4-family, they exhibit distinct differences in ion dependency, transport function, pharmacological properties, and interactions with other proteins. In epithelia, NCBTs are involved in transcellular movement of acid-base equivalents and intracellular pH control. In nonepithelial tissues, NCBTs contribute to intracellular pH regulation; and hence, they are crucial for diverse tissue functions including neuronal discharge, sensory neuron development, performance of the heart, and vascular tone regulation. The function and expression levels of the NCBTs are generally sensitive to intracellular and systemic pH. Animal models have revealed pathophysiological roles of the transporters in disease states including metabolic acidosis, hypertension, visual defects, and epileptic seizures. Studies are being conducted to understand the physiological consequences of genetic polymorphisms in the SLC4-members, which are associated with cancer, hypertension, and drug addiction. Here, we describe the current knowledge regarding the function, structure, and regulation of the mammalian cation-coupled HCO3− transporters of the SLC4-family.

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Electroneutral K+/HCO3- cotransport in cells of medullary thick ascending limb of rat kidney.

Cited by 46 publications

References 27 publications

Basolateral membrane Cl⁻-, Na⁺-, and K⁺-coupled base transport mechanisms in rat MTALH

Basolateral membrane Cl⁻-, Na⁺-, and K⁺-coupled base transport mechanisms in rat MTALH

Acid pH Increases the Stability of BSC1/NKCC2 mRNA in the Medullary Thick Ascending Limb

Cation‐Coupled Bicarbonate Transporters

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Electroneutral K+/HCO3- cotransport in cells of medullary thick ascending limb of rat kidney.

Cited by 46 publications

References 27 publications

Basolateral membrane Cl−-, Na+-, and K+-coupled base transport mechanisms in rat MTALH

Basolateral membrane Cl−-, Na+-, and K+-coupled base transport mechanisms in rat MTALH

Acid pH Increases the Stability of BSC1/NKCC2 mRNA in the Medullary Thick Ascending Limb

Cation‐Coupled Bicarbonate Transporters

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Basolateral membrane Cl⁻-, Na⁺-, and K⁺-coupled base transport mechanisms in rat MTALH

Basolateral membrane Cl⁻-, Na⁺-, and K⁺-coupled base transport mechanisms in rat MTALH