Kinetic properties of the sodium bicarbonate (carbonate) symport in monkey kidney epithelial cells (BSC-1). Interactions between Na+, HCO-3, and pH.

Jentsch, Thomas J.; Schwartz, Peter J.; Schill, B S; Langner, B; Lepple, A P; Keller, Svea K.; Wiederholt, Michael

doi:10.1016/s0021-9258(18)67438-1

Cited by 39 publications

(4 citation statements)

References 24 publications

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“…Previous authors have attempted to distinguish HCO 3 2 versus CO 3 5 transport using either kinetics or supposed CO 3 5 surrogates. Although kinetic approaches [42][43][44][45][46] support the involvement of the NaCO 3 2 ion pair, they cannot be definitive. Work with SO 3 5 or NO 3 2 as CO 3 5 surrogates 47,48 suffer from the drawback that neither mimics both the structure and charge of CO 3…”

Section: Discussionmentioning

confidence: 99%

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Distinguishing among HCO3 −, CO3 =, and H+ as Substrates of Proteins That Appear To Be “Bicarbonate” Transporters

Lee

Occhipinti

Moss

et al. 2022

JASN

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BackgroundDifferentiating among HCO3−, CO3=, and H+movements across membranes has long seemed impossible. We now seek to discriminate unambiguously among three alternate mechanisms: the inward flux of 2 HCO3−(mechanism 1), the inward flux of 1 CO3=(mechanism 2), and the CO2/HCO3−-stimulated outward flux of 2 H+(mechanism 3).MethodsAs a test case, we use electrophysiology and heterologous expression inXenopusoocytes to examine SLC4 family members that appear to transport “bicarbonate” (“HCO3−”).ResultsFirst, we note that cell-surface carbonic anhydrase should catalyze the forward reaction CO2+OH–→HCO3−if HCO3−is the substrate; if it is not, the reverse reaction should occur. Monitoring changes in cell-surface pH (ΔpHS) with or without cell-surface carbonic anhydrase, we find that the presumed Cl-“HCO3” exchanger AE1 (SLC4A1) does indeed transport HCO3−(mechanism 1) as long supposed, whereas the electrogenic Na/“HCO3” cotransporter NBCe1 (SLC4A4) and the electroneutral Na+-driven Cl-“HCO3” exchanger NDCBE (SLC4A8) do not. Second, we use mathematical simulations to show that each of the three mechanisms generates unique quantities of H+at the cell surface (measured asΔpHS) per charge transported (measured as change in membrane current,ΔIm). Calibrating ΔpHS/ΔImin oocytes expressing the H+channel HV1, we find that our NBCe1 data align closely with predictions of CO3=transport (mechanism 2), while ruling out HCO3−(mechanism 1) and CO2/HCO3−-stimulated H+transport (mechanism 3).ConclusionsOur surface chemistry approach makes it possible for the first time to distinguish among HCO3−, CO3=, and H+fluxes, thereby providing insight into molecular actions of clinically relevant acid-base transporters and carbonic-anhydrase inhibitors.

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Section: Discussionmentioning

confidence: 99%

“…[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] 2023. doi: https://doi.org/10.1681/ASN.2022030289…”

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Distinguishing among HCO3 −, CO3 =, and H+ as Substrates of Proteins That Appear To Be “Bicarbonate” Transporters

Lee

Occhipinti

Moss

et al. 2022

JASN

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“…Distinguishing among them has been challenging because, in contrast with non-labile ions (e.g., sodium, potassium), the solutes of reactions (2) and (3) are interchangeable (i.e., they can be converted into each other), making direct measurements virtually impossible. Some investigators have resorted to surrogate substrates or kinetic approaches [ 60 , 61 , 62 , 63 , 64 , 65 , 66 ]. However, neither approaches are definitive: (i) No surrogate can mimic the real physicochemical properties of the substrates under consideration [ 67 ].…”

Section: Carbonic Anhydrases and The Identification Of Substrates Of ...mentioning

confidence: 99%

Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney

Lee

Boron

Occhipinti

2023

IJMS

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Carbonic anhydrases (CAs), because they catalyze the interconversion of carbon dioxide (CO2) and water into bicarbonate (HCO3−) and protons (H+), thereby influencing pH, are near the core of virtually all physiological processes in the body. In the kidneys, soluble and membrane-associated CAs and their synergy with acid–base transporters play important roles in urinary acid secretion, the largest component of which is the reabsorption of HCO3− in specific nephron segments. Among these transporters are the Na+-coupled HCO3− transporters (NCBTs) and the Cl−-HCO3− exchangers (AEs)—members of the “solute-linked carrier” 4 (SLC4) family. All of these transporters have traditionally been regarded as “HCO3−“ transporters. However, recently our group has demonstrated that two of the NCBTs carry CO32− rather than HCO3− and has hypothesized that all NCBTs follow suit. In this review, we examine current knowledge on the role of CAs and “HCO3−” transporters of the SLC4 family in renal acid–base physiology and discuss how our recent findings impact renal acid secretion, including HCO3− reabsorption. Traditionally, investigators have associated CAs with producing or consuming solutes (CO2, HCO3−, and H+) and thus ensuring their efficient transport across cell membranes. In the case of CO32− transport by NCBTs, however, we hypothesize that the role of membrane-associated CAs is not the appreciable production or consumption of substrates but the minimization of pH changes in nanodomains near the membrane.

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Mechanisms of Basolateral Base Transport in the Renal Proximal Tubule

Frömter

Kondo

2007

Ciba Foundation Symposium 139 ‐ Proton Passage Across Cell Membranes

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Kinetic properties of the sodium bicarbonate (carbonate) symport in monkey kidney epithelial cells (BSC-1). Interactions between Na+, HCO-3, and pH.

Cited by 39 publications

References 24 publications

Distinguishing among HCO3 −, CO3 =, and H+ as Substrates of Proteins That Appear To Be “Bicarbonate” Transporters

Distinguishing among HCO3 −, CO3 =, and H+ as Substrates of Proteins That Appear To Be “Bicarbonate” Transporters

Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney

Mechanisms of Basolateral Base Transport in the Renal Proximal Tubule

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