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HCO(3)(-)-independent conductance with a mutant Na(+)/HCO(3)(-) cotransporter (SLC4A4) in a case of proximal renal tubular acidosis with hypokalaemic paralysis.
Parker MD
,
Qin X
,
Williamson RC
,
Toye AM
,
Boron WF
.
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The renal electrogenic Na(+)/HCO(3)(−) cotransporter (NBCe1-A) contributes to the basolateral step of transepithelial HCO(3)(−) reabsorption in proximal tubule epithelia, contributing to the buffering of blood pH. Elsewhere in the body (e.g. muscle cells) NBCe1 variants contribute to, amongst other processes, maintenance of intracellular pH. Others have described a homozygous mutation in NBCe1 (NBCe1-A p.Ala799Val) in an individual with severe proximal renal tubular acidosis (pRTA; usually associated with defective HCO(3)(−) reabsorption in proximal tubule cells) and hypokalaemic periodic paralysis (hypoPP; usually associated with leaky cation channels in muscle cells). Using biotinylation and two-electrode voltage-clamp on Xenopus oocytes expressing NBCe1, we demonstrate that the mutant NBCe1-A (A(A799V)) exhibits a per-molecule transport defect that probably contributes towards the observed pRTA. Furthermore, we find that A(A799V) expression is associated with an unusual HCO(3)(−)-independent conductance that, if associated with mutant NBCe1 in muscle cells, could contribute towards the appearance of hypokalaemic paralysis in the affected individual. We also study three novel lab mutants of NBCe1-A: p.Ala799Ile, p.Ala799Gly and p.Ala799Ser. All three exhibit a per-molecule transport defect, but only A(A799I) exhibits an A(A799V)-like ion conductance. A(A799G) and A(A799S) exhibit unusual outward rectification in their HCO(3)(−)-dependent conductance and A(A799G) exhibits reduced sensitivity to both DIDS and tenidap. A799G is the first mutation shown to affect the apparent tenidap affinity of NBCe1. Finally we show that A(A799V) and A(A799I), which accumulate poorly in the plasma membrane of oocytes, exhibit signs of abnormal intracellular accumulation in a non-polarized renal cell-line.
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
Abuladze,
Structural organization of the human NBC1 gene: kNBC1 is transcribed from an alternative promoter in intron 3.
2000,
Pubmed
Aoki,
Construction of a fusion protein between protein A and green fluorescent protein and its application to western blotting.
1996,
Pubmed
Bevensee,
An electrogenic Na(+)-HCO(-)(3) cotransporter (NBC) with a novel COOH-terminus, cloned from rat brain.
2000,
Pubmed
,
Xenbase
Bok,
Immunolocalization of electrogenic sodium-bicarbonate cotransporters pNBC1 and kNBC1 in the rat eye.
2001,
Pubmed
Boron,
Intracellular pH regulation in the renal proximal tubule of the salamander. Basolateral HCO3- transport.
1983,
Pubmed
Bruce,
Monovalent cation leaks in human red cells caused by single amino-acid substitutions in the transport domain of the band 3 chloride-bicarbonate exchanger, AE1.
2005,
Pubmed
,
Xenbase
Burnham,
Cloning and functional expression of a human kidney Na+:HCO3- cotransporter.
1997,
Pubmed
Ch'en,
S0859, an N-cyanosulphonamide inhibitor of sodium-bicarbonate cotransport in the heart.
2008,
Pubmed
Choi,
The electrogenicity of the rat sodium-bicarbonate cotransporter NBCe1 requires interactions among transmembrane segments of the transporter.
2007,
Pubmed
,
Xenbase
Choi,
Cloning and characterization of a human electrogenic Na+-HCO-3 cotransporter isoform (hhNBC).
1999,
Pubmed
,
Xenbase
Choi,
Role of glycosylation in the renal electrogenic Na+-HCO3- cotransporter (NBCe1).
2003,
Pubmed
,
Xenbase
Choi,
An electroneutral sodium/bicarbonate cotransporter NBCn1 and associated sodium channel.
2000,
Pubmed
,
Xenbase
Cooper,
Molecular and functional characterization of the electroneutral Na/HCO3 cotransporter NBCn1 in rat hippocampal neurons.
2005,
Pubmed
,
Xenbase
Deda,
Hypopotassemic paralysis: a rare presentation of proximal renal tubular acidosis.
2001,
Pubmed
Demirci,
Proximal renal tubular acidosis and ocular pathology: a novel missense mutation in the gene (SLC4A4) for sodium bicarbonate cotransporter protein (NBCe1).
2006,
Pubmed
,
Xenbase
Diakov,
The disulfonic stilbene DIDS and the marine poison maitotoxin activate the same two types of endogenous cation conductance in the cell membrane of Xenopus laevis oocytes.
2001,
Pubmed
,
Xenbase
Dinour,
A novel missense mutation in the sodium bicarbonate cotransporter (NBCe1/SLC4A4) causes proximal tubular acidosis and glaucoma through ion transport defects.
2004,
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
Francis,
Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not paramyotonia.
2011,
Pubmed
Gawenis,
Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter.
2007,
Pubmed
Grichtchenko,
Extracellular HCO(3)(-) dependence of electrogenic Na/HCO(3) cotransporters cloned from salamander and rat kidney.
2000,
Pubmed
,
Xenbase
Gross,
Structural determinants and significance of regulation of electrogenic Na(+)-HCO(3)(-) cotransporter stoichiometry.
2002,
Pubmed
Guizouarn,
Point mutations involved in red cell stomatocytosis convert the electroneutral anion exchanger 1 to a nonselective cation conductance.
2007,
Pubmed
,
Xenbase
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
Igarashi,
Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities.
1999,
Pubmed
Igarashi,
Novel nonsense mutation in the Na+/HCO3- cotransporter gene (SLC4A4) in a patient with permanent isolated proximal renal tubular acidosis and bilateral glaucoma.
2001,
Pubmed
Inatomi,
Mutational and functional analysis of SLC4A4 in a patient with proximal renal tubular acidosis.
2004,
Pubmed
,
Xenbase
Ko,
AE4 is a DIDS-sensitive Cl(-)/HCO(-)(3) exchanger in the basolateral membrane of the renal CCD and the SMG duct.
2002,
Pubmed
Kristensen,
Expression of Na+/HCO3- co-transporter proteins (NBCs) in rat and human skeletal muscle.
2004,
Pubmed
Lee,
Relief of autoinhibition of the electrogenic Na-HCO(3) [corrected] cotransporter NBCe1-B: role of IRBIT vs.amino-terminal truncation.
2012,
Pubmed
,
Xenbase
Li,
Missense mutations in Na+:HCO3- cotransporter NBC1 show abnormal trafficking in polarized kidney cells: a basis of proximal renal tubular acidosis.
2005,
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
Lo,
Severe metabolic acidosis causes early lethality in NBC1 W516X knock-in mice as a model of human isolated proximal renal tubular acidosis.
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
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
Orchard,
Effects of changes of pH on the contractile function of cardiac muscle.
1990,
Pubmed
Praetorius,
A SCL4A10 gene product maps selectively to the basolateral plasma membrane of choroid plexus epithelial cells.
2004,
Pubmed
Romero,
Expression cloning and characterization of a renal electrogenic Na+/HCO3- cotransporter.
1997,
Pubmed
,
Xenbase
Ruff,
An important piece has been placed in the puzzle of hypokalemic periodic paralysis.
2011,
Pubmed
Satoh,
Localization of Na+-HCO-3 cotransporter (NBC-1) variants in rat and human pancreas.
2003,
Pubmed
Schmitt,
Immunolocalization of the electrogenic Na+-HCO-3 cotransporter in mammalian and amphibian kidney.
1999,
Pubmed
,
Xenbase
Schmitt,
Na/HCO3 cotransporters in rat brain: expression in glia, neurons, and choroid plexus.
2000,
Pubmed
Schweigert,
Voltage dependence of the Na-K ATPase: measurements of ouabain-dependent membrane current and ouabain binding in oocytes of Xenopus laevis.
1988,
Pubmed
,
Xenbase
Sciortino,
Cation and voltage dependence of rat kidney electrogenic Na(+)-HCO(-)(3) cotransporter, rkNBC, expressed in oocytes.
1999,
Pubmed
,
Xenbase
Shirakabe,
IRBIT, an inositol 1,4,5-trisphosphate receptor-binding protein, specifically binds to and activates pancreas-type Na+/HCO3- cotransporter 1 (pNBC1).
2006,
Pubmed
,
Xenbase
Skelton,
Acid-base transport by the renal proximal tubule.
2010,
Pubmed
Sobczak,
Endogenous transport systems in the Xenopus laevis oocyte plasma membrane.
2010,
Pubmed
,
Xenbase
Sokolov,
Ion permeation through a voltage- sensitive gating pore in brain sodium channels having voltage sensor mutations.
2005,
Pubmed
,
Xenbase
Stewart,
Functional characterization and modified rescue of novel AE1 mutation R730C associated with overhydrated cation leak stomatocytosis.
2011,
Pubmed
,
Xenbase
Suzuki,
Functional analysis of a novel missense NBC1 mutation and of other mutations causing proximal renal tubular acidosis.
2008,
Pubmed
,
Xenbase
Suzuki,
Defective membrane expression of the Na(+)-HCO(3)(-) cotransporter NBCe1 is associated with familial migraine.
2010,
Pubmed
,
Xenbase
Takano,
Arabidopsis boron transporter for xylem loading.
2002,
Pubmed
Terhag,
Cave Canalem: how endogenous ion channels may interfere with heterologous expression in Xenopus oocytes.
2010,
Pubmed
,
Xenbase
Thomas,
Effects of high-intensity training on MCT1, MCT4, and NBC expressions in rat skeletal muscles: influence of chronic metabolic alkalosis.
2007,
Pubmed
Tillisch,
Myocardial mechanical responses and ionic exchange in high-sodium perfusate.
1974,
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
Villa-Abrille,
The electrogenic Na+/HCO3- cotransport modulates resting membrane potential and action potential duration in cat ventricular myocytes.
2007,
Pubmed
Weber,
Amiloride-sensitive Na+ conductance in native Xenopus oocytes.
1995,
Pubmed
,
Xenbase
Weber,
Ion currents of Xenopus laevis oocytes: state of the art.
1999,
Pubmed
,
Xenbase
Wu,
A sodium channel knockin mutant (NaV1.4-R669H) mouse model of hypokalemic periodic paralysis.
2011,
Pubmed
Yoshitomi,
Rheogenic sodium-bicarbonate cotransport in the peritubular cell membrane of rat renal proximal tubule.
1985,
Pubmed
Zhu,
Topological location and structural importance of the NBCe1-A residues mutated in proximal renal tubular acidosis.
2010,
Pubmed
