Genomes and Genes
sodium bicarbonate symporters
Summary: Proteins that cotransport sodium ions and bicarbonate ions across cellular membranes.
- Bernardo A, Kear F, Santos A, Ma J, Steplock D, Robey R, et al. Basolateral Na(+)/HCO(3)(-) cotransport activity is regulated by the dissociable Na(+)/H(+) exchanger regulatory factor. J Clin Invest. 1999;104:195-201 pubmed
- Pedrosa R, Gonçalves N, Hopfer U, Jose P, Soares da Silva P. Activity and regulation of Na+-HCO3- cotransporter in immortalized spontaneously hypertensive rat and Wistar-Kyoto rat proximal tubular epithelial cells. Hypertension. 2007;49:1186-93 pubmed..It is concluded that SHR cells are endowed with lower NBC activity than WKY cells, but the former is more resistant to 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulphonic acid and responds better to acidosis. ..
- Schmitt B, Biemesderfer D, Romero M, Boulpaep E, Boron W. Immunolocalization of the electrogenic Na+-HCO-3 cotransporter in mammalian and amphibian kidney. Am J Physiol. 1999;276:F27-38 pubmed
- Shirakabe K, Priori G, Yamada H, Ando H, Horita S, Fujita T, et al. IRBIT, an inositol 1,4,5-trisphosphate receptor-binding protein, specifically binds to and activates pancreas-type Na+/HCO3- cotransporter 1 (pNBC1). Proc Natl Acad Sci U S A. 2006;103:9542-7 pubmed..Also, our findings raise the possibility that the regulation through IRBIT enables NBC1 variants to have different physiological roles. ..
- Millar I, Brown P. NBCe2 exhibits a 3 HCO3(-):1 Na+ stoichiometry in mouse choroid plexus epithelial cells. Biochem Biophys Res Commun. 2008;373:550-4 pubmed publisher..The NBCe2, with this stoichiometry, will mediate the efflux of HCO3(-) and Na(+) from the cell into the cerebrospinal fluid at the apical membrane of the choroid plexus. ..
- Burnham C, Amlal H, Wang Z, Shull G, Soleimani M. Cloning and functional expression of a human kidney Na+:HCO3- cotransporter. J Biol Chem. 1997;272:19111-4 pubmed..6-kilobase mRNA is highly expressed in kidney and pancreas, with detectable levels in brain. Functional studies in transiently transfected HEK-293 cells demonstrate that the cloned transporter mediates Na+:HCO3- cotransport. ..
- Bachmann O, Rossmann H, Berger U, Colledge W, Ratcliff R, Evans M, et al. cAMP-mediated regulation of murine intestinal/pancreatic Na+/HCO3- cotransporter subtype pNBC1. Am J Physiol Gastrointest Liver Physiol. 2003;284:G37-45 pubmed..These studies establish the existence of an intracellular HCO(3)(-) concentration- and cell volume-independent activation of colonic NBC by an increase in intracellular cAMP. ..
- Alvarez B, Loiselle F, Supuran C, Schwartz G, Casey J. Direct extracellular interaction between carbonic anhydrase IV and the human NBC1 sodium/bicarbonate co-transporter. Biochemistry. 2003;42:12321-9 pubmed publisher..The tethering of CAII and CAIV close to the NBC1 HCO(3)(-) transport site maximizes the transmembrane HCO(3)(-) gradient local to NBC1 and thereby activates the transport rate...
- Piermarini P, Kim E, Boron W. Evidence against a direct interaction between intracellular carbonic anhydrase II and pure C-terminal domains of SLC4 bicarbonate transporters. J Biol Chem. 2007;282:1409-21 pubmed..Thus, although an HCO3 metabolon may exist, CA II cannot bind directly to pure SLC4-Ct peptides and can bind to GST-SLC4-Ct fusion proteins only when the CA II is immobilized and the fusion protein is soluble, and not vice versa. ..
- Becker H, Deitmer J. Carbonic anhydrase II increases the activity of the human electrogenic Na+/HCO3- cotransporter. J Biol Chem. 2007;282:13508-21 pubmed..Our results show that the transport capacity of NBCe1 is enhanced by the catalytic activity of CAII, in line with the notion that CAII forms a transport metabolon with NBCe1. ..
- Khandoudi N, Albadine J, Robert P, Krief S, Berrebi Bertrand I, Martin X, et al. Inhibition of the cardiac electrogenic sodium bicarbonate cotransporter reduces ischemic injury. Cardiovasc Res. 2001;52:387-96 pubmed..Our data provide evidence that inhibition of hhNBC, whose role in cardiac pathologies could be amplified by overexpression, represents a novel therapeutic approach for ischemic heart disease. ..
- Weinman E, Evangelista C, Steplock D, Liu M, Shenolikar S, Bernardo A. Essential role for NHERF in cAMP-mediated inhibition of the Na+-HCO3- co-transporter in BSC-1 cells. J Biol Chem. 2001;276:42339-46 pubmed
- Abuladze N, Lee I, Newman D, Hwang J, Boorer K, Pushkin A, et al. Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter. J Biol Chem. 1998;273:17689-95 pubmed..These data demonstrate that pNBC encodes the sodium bicarbonate cotransporter in the mammalian pancreas. pNBC is also expressed at a lower level in several other organs, whereas kNBC is expressed uniquely in kidney. ..
- Moser A, Gangopadhyay A, Bradbury N, Peters K, Frizzell R, Bridges R. Electrogenic bicarbonate secretion by prairie dog gallbladder. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1683-94 pubmed..Basolateral HCO(3)(-) entry is mediated by DNDS-sensitive pNBC1, and the driving force for apical anion secretion is provided by K(+) channel activation. ..
- Choi I, Aalkjaer C, Boulpaep E, Boron W. An electroneutral sodium/bicarbonate cotransporter NBCn1 and associated sodium channel. Nature. 2000;405:571-5 pubmed..Oocytes injected with low levels of NBCn1-B complementary RNA exhibit a Na+ conductance that 4,4-diisothiocyanatostilbene-2,2'-disulphonate stimulates slowly and irreversibly. ..
- Choi I, Romero M, Khandoudi N, Bril A, Boron W. Cloning and characterization of a human electrogenic Na+-HCO-3 cotransporter isoform (hhNBC). Am J Physiol. 1999;276:C576-84 pubmed..We conclude that hhNBC is an electrogenic Na+-HCO-3 cotransporter and that hkNBC is also electrogenic. ..
- Romero M, Boron W. Electrogenic Na+/HCO3- cotransporters: cloning and physiology. Annu Rev Physiol. 1999;61:699-723 pubmed..For example, NBC occurs in pancreas, prostate, brain, heart, small and large intestine, stomach, and epididymis. Finally, there are at least two genes that encode NBC proteins. Possible future directions of research are discussed. ..
- Heyer M, Müller Berger S, Romero M, Boron W, Fromter E. Stoichiometry of the rat kidney Na+-HCO3- cotransporter expressed in Xenopus laevis oocytes. Pflugers Arch. 1999;438:322-9 pubmed
- Amlal H, Burnham C, Soleimani M. Characterization of Na+/HCO-3 cotransporter isoform NBC-3. Am J Physiol. 1999;276:F903-13 pubmed..We further propose that enhanced expression of NBC-3 in severe acid stress could play an important role in cell survival by mediating the influx of HCO-3 into the cells. ..
- Dinour D, Chang M, Satoh J, Smith B, Angle N, Knecht A, et al. A novel missense mutation in the sodium bicarbonate cotransporter (NBCe1/SLC4A4) causes proximal tubular acidosis and glaucoma through ion transport defects. J Biol Chem. 2004;279:52238-46 pubmed
- Li H, Worrell R, Matthews J, Husseinzadeh H, Neumeier L, Petrovic S, et al. Identification of a carboxyl-terminal motif essential for the targeting of Na+-HCO-3 cotransporter NBC1 to the basolateral membrane. J Biol Chem. 2004;279:43190-7 pubmed
- Li H, Szigligeti P, Worrell R, Matthews J, Conforti L, Soleimani M. Missense mutations in Na+:HCO3- cotransporter NBC1 show abnormal trafficking in polarized kidney cells: a basis of proximal renal tubular acidosis. Am J Physiol Renal Physiol. 2005;289:F61-71 pubmed
- Casey J. Why bicarbonate?. Biochem Cell Biol. 2006;84:930-9 pubmed..This review provides a wide-ranging view of the biochemistry of bicarbonate and its membrane transporters, revealing what makes the study of bicarbonate transport such a rewarding activity. ..
- Romero M, Fulton C, Boron W. The SLC4 family of HCO 3 - transporters. Pflugers Arch. 2004;447:495-509 pubmed..SLC4 gene products play important roles in the carriage of CO(2) by erythrocytes, the absorption or secretion of H(+) or HCO(3)(-) by several epithelia, as well as the regulation of cell volume and intracellular pH. ..
- Gross E, Abuladze N, Pushkin A, Kurtz I, Cotton C. The stoichiometry of the electrogenic sodium bicarbonate cotransporter pNBC1 in mouse pancreatic duct cells is 2 HCO(3)(-):1 Na(+). J Physiol. 2001;531:375-82 pubmed..The cotransporter operates with a 2 HCO3-:1 Na+ stoichiometry in these cells, and mediates the transport of bicarbonate into the cell across the basolateral membrane. ..
- Romero M, Fong P, Berger U, Hediger M, Boron W. Cloning and functional expression of rNBC, an electrogenic Na(+)-HCO3- cotransporter from rat kidney. Am J Physiol. 1998;274:F425-32 pubmed..Subsequent removal of Na+ in the presence of CO2/HCO3- causes a depolarization of > 50 mV and a concomitant decrease of pHi. Thus rNBC is in the same newly identified family of Na(+)-linked HCO3- transporters as is aNBC. ..
- Pushkin A, Abuladze N, Lee I, Newman D, Hwang J, Kurtz I. Cloning, tissue distribution, genomic organization, and functional characterization of NBC3, a new member of the sodium bicarbonate cotransporter family. J Biol Chem. 1999;274:16569-75 pubmed..Expression of mNBC3 cRNA in Xenopus laevis oocytes demonstrated that the protein encodes a novel stilbene-insensitive 5-(N-ethyl-N-isopropyl)-amiloride-inhibitable sodium bicarbonate cotransporter. ..
- Romero M, Hediger M, Boulpaep E, Boron W. Expression cloning and characterization of a renal electrogenic Na+/HCO3- cotransporter. Nature. 1997;387:409-13 pubmed
- Gross E, Pushkin A, Abuladze N, Fedotoff O, Kurtz I. Regulation of the sodium bicarbonate cotransporter kNBC1 function: role of Asp(986), Asp(988) and kNBC1-carbonic anhydrase II binding. J Physiol. 2002;544:679-85 pubmed..Although CAII does not affect the transport stoichiometry, it may play an important role in enhancing the flux through the transporter when kNBC1-Ser(982) is unphosphorylated. ..
- Jacobs S, Ruusuvuori E, Sipilä S, Haapanen A, Damkier H, Kurth I, et al. Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability. Proc Natl Acad Sci U S A. 2008;105:311-6 pubmed publisher..Hence, Slc4a10 is a promising pharmacological target for the therapy of epilepsy or elevated intracranial pressure. ..
- Gross E, Kurtz I. Structural determinants and significance of regulation of electrogenic Na(+)-HCO(3)(-) cotransporter stoichiometry. Am J Physiol Renal Physiol. 2002;283:F876-87 pubmed..This cAMP-dependent signaling pathway provides HCO(3)(-) -transporting epithelia with an efficient mechanism for modulating the direction of Na(+)-HCO(3)(-) flux through the cotransporter. ..
- Chen L, Kelly M, Rojas J, Parker M, Gill H, Davis B, et al. Use of a new polyclonal antibody to study the distribution and glycosylation of the sodium-coupled bicarbonate transporter NCBE in rodent brain. Neuroscience. 2008;151:374-85 pubmed..In oocytes, mutating any one of the three consensus N-glycosylation sites reduces glycosylation of the other two, and the triple mutant exhibits negligible functional expression. ..
- Bok D, Schibler M, Pushkin A, Sassani P, Abuladze N, Naser Z, et al. Immunolocalization of electrogenic sodium-bicarbonate cotransporters pNBC1 and kNBC1 in the rat eye. Am J Physiol Renal Physiol. 2001;281:F920-35 pubmed..The data in this study will serve as a basis for understanding the molecular mechanisms responsible for abnormalities in ocular electrogenic sodium-bicarbonate cotransport in patients with mutations in the NBC1 gene. ..
- Brandes A, Oehlke O, Schümann A, Heidrich S, Thevenod F, Roussa E. Adaptive redistribution of NBCe1-A and NBCe1-B in rat kidney proximal tubule and striated ducts of salivary glands during acid-base disturbances. Am J Physiol Regul Integr Comp Physiol. 2007;293:R2400-11 pubmed
- Praetorius J, Nejsum L, Nielsen S. A SCL4A10 gene product maps selectively to the basolateral plasma membrane of choroid plexus epithelial cells. Am J Physiol Cell Physiol. 2004;286:C601-10 pubmed
- Damkier H, Nielsen S, Praetorius J. Molecular expression of SLC4-derived Na+-dependent anion transporters in selected human tissues. Am J Physiol Regul Integr Comp Physiol. 2007;293:R2136-46 pubmed..In conclusion, the selected human tissues display distinct expression patterns of HCO(3)(-) transporters, which closely resemble that of rodent tissues. ..
- Pushkin A, Abuladze N, Newman D, Lee I, Xu G, Kurtz I. Cloning, characterization and chromosomal assignment of NBC4, a new member of the sodium bicarbonate cotransporter family. Biochim Biophys Acta. 2000;1493:215-8 pubmed..The first of two putative stilbene binding motifs (K(M/L)(X)K) is lacking in NBC4 (amino acids 655-658). The approximately 6 kb NBC4 transcript is moderately expressed in heart, with the highest expression in liver, testes and spleen. ..
- Ishibashi K, Sasaki S, Marumo F. Molecular cloning of a new sodium bicarbonate cotransporter cDNA from human retina. Biochem Biophys Res Commun. 1998;246:535-8 pubmed..NBC2 may be a major regulator of extracellular pH of retina where light stimulation produces an extracellular alkalization and may contribute as a solute transporter to the prevention of retinal detachment. ..
- Thevenod F, Roussa E, Schmitt B, Romero M. Cloning and immunolocalization of a rat pancreatic Na(+) bicarbonate cotransporter. Biochem Biophys Res Commun. 1999;264:291-8 pubmed..The data suggest that rpNBC likely plays a more important role in the transport of HCO(-)(3) by rat pancreatic acinar and duct cells than previously believed. ..
- Gill H, Boron W. Preliminary X-ray diffraction analysis of the cytoplasmic N-terminal domain of the Na/HCO3 cotransporter NBCe1-A. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006;62:534-7 pubmed..9 A3 Da(-1), with two monomers of molecular weight approximately 83 kDa in the asymmetric unit. The molecular- replacement packing solution shows that the molecules form dimers by a domain-swapping mechanism. ..
- Turban S, Beutler K, Morris R, Masilamani S, Fenton R, Knepper M, et al. Long-term regulation of proximal tubule acid-base transporter abundance by angiotensin II. Kidney Int. 2006;70:660-8 pubmed..Candesartan also decreased urinary ammonium excretion (P<0.05). The long-term effects of Ang-II in the proximal tubule may be mediated in part by regulation of NBC1 abundance, modifying bicarbonate reabsorption. ..
- Yamada H, Yamazaki S, Moriyama N, Hara C, Horita S, Enomoto Y, et al. Localization of NBC-1 variants in human kidney and renal cell carcinoma. Biochem Biophys Res Commun. 2003;310:1213-8 pubmed..These results indicate that kNBC-1 is the dominant variant that mediates bicarbonate absorption from human renal proximal tubules. They also suggest that NBC-1 may have distinct roles in cancer cells. ..
- Sobrinho C, Goncalves C, Takakura A, Mulkey D, Moreira T. Fluorocitrate-mediated depolarization of astrocytes in the retrotrapezoid nucleus stimulates breathing. J Neurophysiol. 2017;118:1690-1697 pubmed publisher..These results support the possibility that astrocyte depolarization can facilitate purinergic enhancement of respiratory drive from the RTN. ..
- Liu Y, Xu K, Chen L, Sun X, Parker M, Kelly M, et al. Distribution of NBCn2 (SLC4A10) splice variants in mouse brain. Neuroscience. 2010;169:951-64 pubmed publisher..Immunohistochemistry with anti-ABCD shows that NBCn2 is highly expressed in choroid plexus, cortex, molecular layer of cerebellum, hippocampus, and some specific regions of the brainstem. ..
- Chen L, Kelly M, Parker M, Bouyer P, Gill H, Felie J, et al. Expression and localization of Na-driven Cl-HCO(3)(-) exchanger (SLC4A8) in rodent CNS. Neuroscience. 2008;153:162-74 pubmed publisher..Thus, NDCBE is in a position to contribute substantially to pH(i) regulation in multiple CNS neurons. ..
- Sonalker P, Tofovic S, Jackson E. Increased expression of the sodium transporter BSC-1 in spontaneously hypertensive rats. J Pharmacol Exp Ther. 2004;311:1052-61 pubmed..We conclude that increased expression of BSC-1, and to a lesser extent, aquaporin-2, ROMK-1, NHE-3, and NBC-1 may contribute to the pathogenesis of hypertension in the SHR. ..
- Villa Abrille M, Petroff M, Aiello E. The electrogenic Na+/HCO3- cotransport modulates resting membrane potential and action potential duration in cat ventricular myocytes. J Physiol. 2007;578:819-29 pubmed..The above results allow us to conclude that the cardiac electrogenic Na+/HCO3- cotransport has a relevant influence on RMP and APD of cat ventricular cells. ..
- Choi I, Soo Yang H, Boron W. The electrogenicity of the rat sodium-bicarbonate cotransporter NBCe1 requires interactions among transmembrane segments of the transporter. J Physiol. 2007;578:131-42 pubmed..Thus, these chimeras were electroneutral, as were two others consisting of NBCe1(Nt-L)/NBCn1(TM6-Ct) and NBCn1(Nt-L)/NBCe1(TM6-Ct). We propose that the electrogenicity of NBCe1 requires interactions between TM1-5 and TM6-13. ..
- Alvarez B, Vithana E, Yang Z, Koh A, Yeung K, Yong V, et al. Identification and characterization of a novel mutation in the carbonic anhydrase IV gene that causes retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2007;48:3459-68 pubmed..This study indicates that, as with European patients with RP, mutations in CA4 also account for <or=1% of Chinese patients with RP. ..
- Carlin R, Quesnell R, Zheng L, Mitchell K, Schultz B. Functional and molecular evidence for Na(+)-HCO cotransporter in porcine vas deferens epithelia. Am J Physiol Cell Physiol. 2002;283:C1033-44 pubmed
- Alper S. Genetic diseases of acid-base transporters. Annu Rev Physiol. 2002;64:899-923 pubmed..Study of acid-base transport disease-associated mutations should enhance our understanding of protein structure-function relationships and their impact on the physiology of cell, tissue, and organism. ..
- Adijanto J, Banzon T, Jalickee S, Wang N, Miller S. CO2-induced ion and fluid transport in human retinal pigment epithelium. J Gen Physiol. 2009;133:603-22 pubmed publisher..This homeostatic process would preserve the close anatomical relationship between photoreceptor outer segments and RPE in the dark and light, thus protecting the health of the photoreceptors. ..
- Chang M, DiPiero J, SONNICHSEN F, Romero M. Entry to "formula tunnel" revealed by SLC4A4 human mutation and structural model. J Biol Chem. 2008;283:18402-10 pubmed publisher..These results contrast the current understanding of the AE1 N terminus as protein-binding sites and propose that hkNBCe1 (and other SLC4) cytoplasmic N termini play roles in controlling HCO(3)(-) permeation. ..
- Becker H, Deitmer J. Voltage dependence of H+ buffering mediated by sodium bicarbonate cotransport expressed in Xenopus oocytes. J Biol Chem. 2004;279:28057-62 pubmed..Our results indicate that the electrogenic NBCe1 renders the cell membrane potential an effective regulator of intracellular H(+) buffering and acid/base-coupled metabolite transport. ..
- Takeuchi T, Ham M, Mizumori M, Guth P, Engel E, Kaunitz J, et al. Solute diffusion through stripped mouse duodenum. J Physiol Pharmacol. 2007;58:767-91 pubmed..Limited viability of the villous cells and impaired structural stability of the villi further limit long-term, villous cell functional studies of mucosal preparations mounted in small aperture diffusion chambers. ..
- Melkikh A, Sutormina M. Model of active transport of ions in cardiac cell. J Theor Biol. 2008;252:247-54 pubmed publisher..The calculated internal concentrations of ions are in good agreement with the corresponding experimental values. ..
- Damkier H, Nielsen S, Praetorius J. An anti-NH2-terminal antibody localizes NBCn1 to heart endothelia and skeletal and vascular smooth muscle cells. Am J Physiol Heart Circ Physiol. 2006;290:H172-80 pubmed..The NBCn1 is a likely candidate for mediating the reported electroneutral Na+-HCO3(-) cotransport in vascular smooth muscle. ..
- Müller Berger S, Ducoudret O, Diakov A, Fromter E. The renal Na-HCO3-cotransporter expressed in Xenopus laevis oocytes: change in stoichiometry in response to elevation of cytosolic Ca2+ concentration. Pflugers Arch. 2001;442:718-28 pubmed..This is more likely than the induction of a new transport pouch for a third (HCO3-) ion, which would require exceedingly large conformational changes of the transport protein. ..
- Bachmann O, Franke K, Yu H, Riederer B, Li H, Soleimani M, et al. cAMP-dependent and cholinergic regulation of the electrogenic intestinal/pancreatic Na+/HCO3- cotransporter pNBC1 in human embryonic kidney (HEK293) cells. BMC Cell Biol. 2008;9:70 pubmed publisher..Regulation of pNBC1 by secretagogues appears to be not solely dependent on its primary structure, but also on properties of the cell type in which it is expressed. ..
- Alper S. Molecular physiology and genetics of Na+-independent SLC4 anion exchangers. J Exp Biol. 2009;212:1672-83 pubmed publisher..A growing body of structure-function and interaction data, together with emerging information about physiological function and structure, is advancing our understanding of SLC4 anion exchangers. ..
- Kim Y, Verlander J, Matthews S, Kurtz I, Shin W, Weiner I, et al. Intercalated cell H+/OH- transporter expression is reduced in Slc26a4 null mice. Am J Physiol Renal Physiol. 2005;289:F1262-72 pubmed..Reduced intercalated cell H(+)/OH(-) transporter expression is observed in Slc26a4 null mice, which likely attenuates the rise in intracellular and systemic pH expected with genetic disruption of Slc26a4. ..
- Rauth R, Potter K, Ngan A, Saad D, Mehr R, Luong V, et al. Dental enamel: genes define biomechanics. J Calif Dent Assoc. 2009;37:863-8 pubmed
- Astion M, Orkand R. Electrogenic Na+/HCO3- cotransport in neuroglia. Glia. 1988;1:355-7 pubmed..These observations indicate the presence in the glial membrane of an electrogenic Na+/HCO3- cotransporter in which the stoichiometry of HCO3- to Na+ is greater than 1. ..
- Niederer S, Swietach P, Wilson D, Smith N, Vaughan Jones R. Measuring and modeling chloride-hydroxyl exchange in the Guinea-pig ventricular myocyte. Biophys J. 2008;94:2385-403 pubmed..Irrespective of ionic mechanism, CHE's pH sensitivity helps to define resting intracellular pH, and hence basal function in the heart. ..
- Seidler U, Rossmann H, Jacob P, Bachmann O, Christiani S, Lamprecht G, et al. Expression and function of Na+HCO3- cotransporters in the gastrointestinal tract. Ann N Y Acad Sci. 2000;915:1-14 pubmed