Cellular Mechanisms of Renal Tubular Acidification

Hamm, L. Lee; Alpern, Robert J.; Preisig, Patricia A.

doi:10.1016/b978-0-12-381462-3.00055-0

Cited by 23 publications

(17 citation statements)

References 458 publications

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“…Consequently, the decrease of H + flux in the proximal tubule when inhibited by EIPA is in line with NHE-mediated apical proton secretion. Alternatively or additionally, EIPA may have blocked a different isoform of NHE, for example NHE1 that appears to be expressed in the basolateral membrane of the proximal tubules in mammals (Hamm et al, 2013;Bobulescu et al, 2005). NHE may be present in the distal segment of goldfish renal tubule, but in accordance with our measurements is probably not involved in acid-base regulation in this region, as has also been suggested for the mammalian distal tubule (Hamm et al, 2013).…”

Section: Effects Of Ion Transporter Inhibitors Targeting Epithelial Tsupporting

confidence: 88%

“…They are, however, likely to play a role in acid-base regulation, so we have incorporated them into our proposed models where appropriate. The models take into account inhibitor results from the present study, protein and mRNA expression data from Fehsenfeld and Wood (2018), as well as aspects from the mammalian models for renal acid-base (Hamm et al, 2013) and ammonia transport Verlander, 2013, 2017). While depicted here as one cell, it is possible that certain processes are instead associated with multiple, rather specific cell types as in the mammalian system.…”

Section: Effects Of Ion Transporter Inhibitors Targeting Epithelial Tmentioning

confidence: 99%

“…While depicted here as one cell, it is possible that certain processes are instead associated with multiple, rather specific cell types as in the mammalian system. NHE NHE is generally believed to promote apical H + secretion (and Na + absorption) in the vertebrate kidney and specifically in the proximal tubule as the major site for renal acid excretion (Gilmour and Perry, 2009; Hamm et al, 2013;Ivanis et al 2008;Teranishi et al 2013). Furthermore, protein abundance of NHE (isoform 3) in the cortical brush-border apical membrane of the proximal tubule was reported to increase following chronic metabolic acidosis in rats (Ambühl et al, 1996).…”

Section: Effects Of Ion Transporter Inhibitors Targeting Epithelial Tmentioning

confidence: 99%

“…An electrogenic Na + /HCO 3 − co-transporter (NBCe1A/NBC1) in basolateral membranes of the proximal tubule is crucial for the reabsorption of base in mammals (Hamm et al, 2013;Weiner and Verlander, 2013;Handlogten et al, 2015). NBC1 has also been identified in the trout kidney and was proposed to mediate increased basolateral reabsorption of HCO 3 − in response to a respiratory acidosis caused by hypercarbia (Perry et al, 2003a).…”

Section: Hco 3 − Transportersmentioning

confidence: 99%

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Section-specific H+ fluxes in renal tubules of fasted and fed goldfish

Fehsenfeld

Kolosov

Wood

2019

Journal of Experimental Biology

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A recent study demonstrated that in response to a feeding-induced metabolic acidosis, goldfish (Carassius auratus) adjust epithelial protein and/or mRNA expression in their kidney tubules for multiple transporters known to be relevant for acid-base regulation. These include Na + /H + exchanger (NHE), V-type H + -ATPase (V-ATPase), cytoplasmic carbonic anhydrase, HCO 3 − transporters and Rhesus proteins. Consequently, renal acid output in the form of protons and NH 4 + increases. However, little is known about the mechanistic details of renal acid-base regulation in C. auratus and teleost fishes in general. The present study applied the scanning ion-selective electrode technique (SIET) to measure proton flux in proximal, distal and connecting tubules of goldfish. We detected increased H + efflux into the extracellular fluid from the tubule in fed animals, resulting from paracellular back-flux of H + through the tight junction. By applying inhibitors for selected acid-base regulatory epithelial transporters, we found that cytosolic carbonic anhydrase and HCO 3 − transporters were important in mediating H + flux in all three tubule segments of fed goldfish. Contrastingly, V-ATPase seemed to play a role in H + flux only in proximal and distal tubules, and NHE in proximal and connecting tubules. We developed working models for transport of acid-base relevant equivalents (H + , HCO 3 − , NH 3 /NH 4 + ) for each tubule segment in C. auratus kidney. While the proximal tubule appears to play a major role in both H + secretion and HCO 3 − reabsorption, the distal and connecting tubules seem to mainly serve for HCO 3 − reabsorption and NH 3 /NH 4 + secretion.

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Section: Effects Of Ion Transporter Inhibitors Targeting Epithelial Tsupporting

confidence: 88%

Section: Effects Of Ion Transporter Inhibitors Targeting Epithelial Tmentioning

confidence: 99%

Section: Effects Of Ion Transporter Inhibitors Targeting Epithelial Tmentioning

confidence: 99%

Section: Hco 3 − Transportersmentioning

confidence: 99%

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Section-specific H+ fluxes in renal tubules of fasted and fed goldfish

Fehsenfeld

Kolosov

Wood

2019

Journal of Experimental Biology

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“…The defect in bicarbonate absorption can be isolated (Table 1) or accompanied by additional proximal tubule transport defects (Table 2). Proximal tubular bicarbonate absorption is an indirect process mediated by the coupling of apical NHE3 (to a lesser extent the apical H + -ATPase) and basolateral NBCe1-A transport (Fig.4A; [16, 44]. The rate of bicarbonate absorption is enhanced by membrane bound CAIV and cytoplasmic CAII that catalyze the hydration/dehydration of CO 2 in the lumen and cytoplasm respectively.…”

Section: Familial Isolated Proximal Renal Tubular Acidosismentioning

confidence: 99%

NBCe1 as a model carrier for understanding the structure–function properties of Na+-coupled SLC4 transporters in health and disease

Kurtz¹

2014

Pflugers Arch - Eur J Physiol

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SLC4 transporters are membrane proteins that in general mediate the coupled transport of bicarbonate (carbonate) and share amino acid sequence homology. These proteins differ as to whether they also transport Na+ and/or Cl−, in addition to their charge transport stoichiometry, membrane targeting, substrate affinities, developmental expression, regulatory motifs, and protein-protein interactions. These differences account in part for the fact that functionally, SLC4 transporters have various physiological roles in mammals including transepithelial bicarbonate transport, intracellular pH regulation, transport of Na+ and/or Cl−, and possibly water. Bicarbonate transport is not unique to the SLC4 family since the structurally unrelated SLC26 family has at least three proteins that mediate Cl−-HCO3− exchange. The present review focuses on the first of the sodium-dependent SLC4 transporters that was identified whose structure has been most extensively studied: the electrogenic Na+-base cotransporter NBCe1. Mutations in NBCe1 cause proximal renal tubular acidosis (pRTA) with neurologic and ophthalmologic extrarenal manifestations. Recent studies have characterized important structure-function properties of the transporter and how they are perturbed as a result of mutations that cause pRTA. It has become increasingly apparent that the structure of NBCe1 differs in several key features from the SLC4 Cl−-HCO3− exchanger AE1 whose structural properties have been well-studied. In this review, the structure-function properties and regulation of NBCe1 will be highlighted and its role in health and disease will be reviewed in detail.

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NBCe1 Electrogenic Na+-Coupled HCO3 -(CO3 2-) Transporter

Kurtz¹

2016

Encyclopedia of Signaling Molecules

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Cellular Mechanisms of Renal Tubular Acidification

Cited by 23 publications

References 458 publications

Section-specific H+ fluxes in renal tubules of fasted and fed goldfish

Section-specific H+ fluxes in renal tubules of fasted and fed goldfish

NBCe1 as a model carrier for understanding the structure–function properties of Na+-coupled SLC4 transporters in health and disease

NBCe1 Electrogenic Na+-Coupled HCO3 -(CO3 2-) Transporter

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