Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
In the basolateral membrane of proximal-tubule cells, NBCe1-A (SLC4A4, variant A), operating with an apparent Na(+):HCO(3)(-) stoichiometry of 1:3, contributes to the reclamation of HCO(3)(-) from the glomerular filtrate, thereby preventing whole body acidosis. Others have reported that NBCe1-like activity in human, rabbit, and rat renal preparations is substantially influenced by lithium, sulfite, oxalate, and harmaline. These data were taken as evidence for the presence of distinct Na(+) and CO(3)(2-) binding sites in NBCe1-A, favoring a model of 1 Na(+):1 HCO(3)(-):1 CO(3)(2-). Here, we reexamine these findings by expressing human or rabbit NBCe1-A clones in Xenopus oocytes. In oocytes, NBCe1-A exhibits a 1:2 stoichiometry and could operate in one of five thermodynamically equivalent transport modes: 1) cotransport of Na(+) + 2 HCO(3)(-), 2) cotransport of Na(+) + CO(3)(2-), 3) transport of NaCO(3)(-), 4) exchange of Na(+) + HCO(3)(-) for H(+), or 5) HCO(3)(-)-activated exchange of Na(+) for 2 H(+). In contrast to the behavior of NBCe1-like activity in renal preparations, we find that cloned NBCe1-A is only slightly stimulated by Li(+), not at all influenced by sulfite or oxalate, and only weakly inhibited by harmaline. These negative data do not uniquely support any of the five models above. In addition, we find that NBCe1-A mediates a small amount of Na(+)-independent NO(3)(-) transport and that NBCe1-A is somewhat inhibited by extracellular benzamil. We suggest that the features of NBCe1-like activity in renal preparations are influenced by yet-to-be-identified renal factors. Thus the actual ionic substrates of NBCe1 remain to be identified.
Abuladze,
Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter.
1998, Pubmed,
Xenbase
Abuladze,
Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter.
1998,
Pubmed
,
Xenbase Akiba,
Electrogenic sodium/bicarbonate cotransport in rabbit renal cortical basolateral membrane vesicles.
1986,
Pubmed Alvarado,
The effect of harmaline on intestinal sodium transport and on sodium-dependent D-glucose transport in brush-border membrane vesicles from rabbit jejunum.
1979,
Pubmed Amlal,
Functional characterization of a cloned human kidney Na+:HCO3- cotransporter.
1998,
Pubmed Aronson,
Harmaline inhibition of Na-dependent transport in renal microvillus membrane vesicles.
1980,
Pubmed Bevensee,
An electrogenic Na(+)-HCO(-)(3) cotransporter (NBC) with a novel COOH-terminus, cloned from rat brain.
2000,
Pubmed
,
Xenbase Boron,
Intracellular pH-regulating mechanism of the squid axon. Relation between the external Na+ and HCO-3 dependences.
1985,
Pubmed Boron,
Intracellular pH regulation in the renal proximal tubule of the salamander. Basolateral HCO3- transport.
1983,
Pubmed Boron,
Modular structure of sodium-coupled bicarbonate transporters.
2009,
Pubmed Burnham,
Cloning and functional expression of a human kidney Na+:HCO3- cotransporter.
1997,
Pubmed Choi,
An electroneutral sodium/bicarbonate cotransporter NBCn1 and associated sodium channel.
2000,
Pubmed
,
Xenbase Choi,
Role of glycosylation in the renal electrogenic Na+-HCO3- cotransporter (NBCe1).
2003,
Pubmed
,
Xenbase Ducoudret,
The renal Na-HCO3-cotransporter expressed in Xenopus laevis oocytes: inhibition by tenidap and benzamil and effect of temperature on transport rate and stoichiometry.
2001,
Pubmed
,
Xenbase Grassl,
Na+/HCO3-co-transport in basolateral membrane vesicles isolated from rabbit renal cortex.
1986,
Pubmed Grassl,
HCO3- transport in basolateral membrane vesicles isolated from rat renal cortex.
1987,
Pubmed Grichtchenko,
Cloning, characterization, and chromosomal mapping of a human electroneutral Na(+)-driven Cl-HCO3 exchanger.
2001,
Pubmed
,
Xenbase Grichtchenko,
Extracellular HCO(3)(-) dependence of electrogenic Na/HCO(3) cotransporters cloned from salamander and rat kidney.
2000,
Pubmed
,
Xenbase Gross,
The stoichiometry of the electrogenic sodium bicarbonate cotransporter NBC1 is cell-type dependent.
2001,
Pubmed Heyer,
Stoichiometry of the rat kidney Na+-HCO3- cotransporter expressed in Xenopus laevis oocytes.
1999,
Pubmed
,
Xenbase Horita,
Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities.
2005,
Pubmed
,
Xenbase Humphreys,
Functional characterization and regulation by pH of murine AE2 anion exchanger expressed in Xenopus oocytes.
1994,
Pubmed
,
Xenbase Igarashi,
Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities.
1999,
Pubmed Kao,
Oligomeric structure and minimal functional unit of the electrogenic sodium bicarbonate cotransporter NBCe1-A.
2008,
Pubmed Karniski,
Immunolocalization of sat-1 sulfate/oxalate/bicarbonate anion exchanger in the rat kidney.
1998,
Pubmed Krick,
Ability of sat-1 to transport sulfate, bicarbonate, or oxalate under physiological conditions.
2009,
Pubmed
,
Xenbase Lee,
Relief of autoinhibition of the electrogenic Na-HCO(3) [corrected] cotransporter NBCe1-B: role of IRBIT vs.amino-terminal truncation.
2012,
Pubmed
,
Xenbase Liu,
Cloning and identification of two novel NBCe1 splice variants from mouse reproductive tract tissues: a comparative study of NCBT genes.
2011,
Pubmed Lu,
Reversible and irreversible interactions of DIDS with the human electrogenic Na/HCO3 cotransporter NBCe1-A: role of lysines in the KKMIK motif of TM5.
2007,
Pubmed
,
Xenbase Maunsbach,
Immunoelectron microscopic localization of the electrogenic Na/HCO(3) cotransporter in rat and ambystoma kidney.
2000,
Pubmed McAlear,
Electrogenic Na/HCO3 cotransporter (NBCe1) variants expressed in Xenopus oocytes: functional comparison and roles of the amino and carboxy termini.
2006,
Pubmed
,
Xenbase Musa-Aziz,
Using fluorometry and ion-sensitive microelectrodes to study the functional expression of heterologously-expressed ion channels and transporters in Xenopus oocytes.
2010,
Pubmed
,
Xenbase Parker,
Characterization of human SLC4A10 as an electroneutral Na/HCO3 cotransporter (NBCn2) with Cl- self-exchange activity.
2008,
Pubmed
,
Xenbase Parker,
HCO(3)(-)-independent conductance with a mutant Na(+)/HCO(3)(-) cotransporter (SLC4A4) in a case of proximal renal tubular acidosis with hypokalaemic paralysis.
2012,
Pubmed
,
Xenbase Parker,
The divergence, actions, roles, and relatives of sodium-coupled bicarbonate transporters.
2013,
Pubmed Romero,
The SLC4 family of HCO 3 - transporters.
2004,
Pubmed Romero,
Expression cloning and characterization of a renal electrogenic Na+/HCO3- cotransporter.
1997,
Pubmed
,
Xenbase Romero,
Cloning and functional expression of rNBC, an electrogenic Na(+)-HCO3- cotransporter from rat kidney.
1998,
Pubmed
,
Xenbase Ruiz,
The renal cortical Na-HCO3 cotransporter: V. expression in Xenopus oocytes.
1996,
Pubmed
,
Xenbase Samarzija,
The mechanism of action of harmaline on renal solute transport.
1977,
Pubmed Schmitt,
Immunolocalization of the electrogenic Na+-HCO-3 cotransporter in mammalian and amphibian kidney.
1999,
Pubmed
,
Xenbase Sciortino,
Cation and voltage dependence of rat kidney electrogenic Na(+)-HCO(-)(3) cotransporter, rkNBC, expressed in oocytes.
1999,
Pubmed
,
Xenbase Seki,
The Na(+)-HCO3- cotransporter operates with a coupling ratio of 2 HCO3- to 1 Na+ in isolated rabbit renal proximal tubule.
1993,
Pubmed Sepúlveda,
Harmaline, a potent inhibitor of sodium-dependent transport.
1974,
Pubmed Skelton,
Acid-base transport by the renal proximal tubule.
2010,
Pubmed Soleimani,
Ionic mechanism of Na+-HCO3- cotransport in rabbit renal basolateral membrane vesicles.
1989,
Pubmed Soleimani,
Cation specificity and modes of the Na+:CO3(2-):HCO3- cotransporter in renal basolateral membrane vesicles.
1991,
Pubmed Soleimani,
Stoichiometry of Na+-HCO-3 cotransport in basolateral membrane vesicles isolated from rabbit renal cortex.
1987,
Pubmed Toye,
The human NBCe1-A mutant R881C, associated with proximal renal tubular acidosis, retains function but is mistargeted in polarized renal epithelia.
2006,
Pubmed
,
Xenbase Trudeau,
HERG, a human inward rectifier in the voltage-gated potassium channel family.
1995,
Pubmed Virkki,
Cloning of a Na+-driven Cl/HCO3 exchanger from squid giant fiber lobe.
2003,
Pubmed
,
Xenbase Yoshitomi,
Rheogenic sodium-bicarbonate cotransport in the peritubular cell membrane of rat renal proximal tubule.
1985,
Pubmed