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NBCe1, an Electrogenic Na+ Bicarbonate Cotransporter, in Epithelia

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Book cover Ion Channels and Transporters of Epithelia in Health and Disease

Part of the book series: Physiology in Health and Disease ((PIHD))

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Abstract

Na+/bicarbonate (HCO3 −) cotransporters (NBCs) are involved in maintaining both cellular and systemic pH homeostasis. Thus far, NBCs are found in the SLC4 gene family, which also includes Na+-independent anion exchangers. Of the ten SLC4 genes, five genes are Na+ bicarbonate cotransport systems: 2 electrogenic transporters, NBCe1 and 2 (SLC4A4 and A5); 2 electroneutral, NBCn1 and 2 (SLC4A7 and A8); and a Na+-driven Cl−/HCO3 − exchanger (NDCBE; SLC4A10). There are five NBCe1 isoforms: NBCe1-A (kidney isoform), NBCe1-B (pancreatic and general isoform), NBCe1-C (brain isoform), NBCe1-D, and NBCe1-E (unknown localization). Malfunction of NBCe1 transporters in epithelial cells leads to inappropriate bicarbonate transport and cellular buffering. In humans, recessive NBCe1 (SLC4A4; OMIM #603345) mutations cause development of proximal renal tubular acidosis (pRTA), cataracts, glaucoma, and defective tooth enamel with occasional occurrence of intestinal obstruction. This chapter will focus on physiological and pathological NBCe1 protein function in epithelial tissues, especially those resulting in human disease.

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Notes

  1. 1.

    Δμ ion = RT•ln{[ion]inside/[ion]outside} + zFΔΨ.

  2. 2.

    “z” is the net charge on a molecule, F is the Faraday constant, and ΔΨ = Ψ(inside) − Ψ(outside), which is also equal to the membrane potential (V m ).

  3. 3.

    “R” is the gas constant, “T” is temperature in Kelvin degrees, and “ln” is the natural log.

References

  • Abuladze N, Lee I, Newman D, Hwang J, Boorer K, Pushkin A, Kurtz I (1998) Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter. J Biol Chem 273(28):17689–17695

    Article  CAS  PubMed  Google Scholar 

  • Abuladze N, Song M, Pushkin A, Newman D, Lee I, Nicholas S, Kurtz I (2000) Structural organization of the human NBC1 gene: kNBC1 is transcribed from an alternative promoter in intron 3. Gene 251(2):109–122

    Article  CAS  PubMed  Google Scholar 

  • Alper SL (1991) The band 3-related anion exchanger (AE) gene family. Annu Rev Physiol 53:549–564

    Article  CAS  PubMed  Google Scholar 

  • Amlal H, Wang Z, Burnham C, Soleimani M (1998) Functional characterization of a cloned human kidney Na+:HCO3 − cotransporter. J Biol Chem 273(27):16810–16815

    Article  CAS  PubMed  Google Scholar 

  • Bachmann O, Rossmann H, Berger UV, Colledge WH, Ratcliff R, Evans MJ, Gregor M, Seidler U (2003) cAMP-mediated regulation of murine intestinal/pancreatic Na+/HCO3 − cotransporter subtype pNBC1. Am J Physiol Gastrointest Liver Physiol 284(1):G37–G45

    Article  CAS  PubMed  Google Scholar 

  • Bachmann O, Reichelt D, Tuo B, Manns MP, Seidler U (2006) Carbachol increases Na+/HCO3 − cotransport activity in murine colonic crypts in a M3-, Ca2+/calmodulin-, and PKC-dependent manner. Am J Physiol Gastrointest Liver Physiol 291(4):G650–G657

    Article  CAS  PubMed  Google Scholar 

  • Banales JM, Saez E, Uriz M, Sarvide S, Urribarri AD, Splinter P, Tietz Bogert PS, Bujanda L, Prieto J, Medina JF et al (2012) Upregulation of mir-506 leads to decreased AE2 expression in biliary epithelium of patients with primary biliary cirrhosis. Hepatology 56(2):687–697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bartolo RC, Harfoot N, Gill M, McLeod BJ, Butt AG (2009) Secretagogues stimulate electrogenic HCO3 − secretion in the ileum of the brushtail possum, Trichosurus vulpecula: evidence for the role of a Na+/HCO3 − cotransporter. J Exp Biol 212(Pt 16):2645–2655

    Article  CAS  PubMed  Google Scholar 

  • Becker HM, Deitmer JW (2004) Voltage dependence of H+ buffering mediated by sodium bicarbonate cotransport expressed in Xenopus oocytes. J Biol Chem 279(27):28057–28062

    Article  CAS  PubMed  Google Scholar 

  • Bevensee MO, Schmitt BM, Choi I, Romero MF, Boron WF (2000) An electrogenic Na/HCO3 cotransporter (NBC) with a novel C terminus, cloned from rat brain. Am J Physiol Cell Physiol 278(6):C1200–C1211

    CAS  PubMed  Google Scholar 

  • Bok D, Schibler MJ, Pushkin A, Sassani P, Abuladze N, Naser Z, Kurtz I (2001) Immunolocalization of electrogenic sodium-bicarbonate cotransporters pNBC1 and kNBC1 in the rat eye. Am J Physiol Renal Physiol 281(5):F920–F935

    CAS  PubMed  Google Scholar 

  • Boron WF (1986) Intracellular pH regulation in epithelial cells. Annu Rev Physiol 48:377–388

    Article  CAS  PubMed  Google Scholar 

  • Boron WF (1992) Control of intracellular pH. In: Seldin DW, Giebisch G (eds) The kidney: physiology and pathophysiology, 2nd edn. Raven, New York

    Google Scholar 

  • Boron WF, Boulpaep EL (2003) Medical physiology. Saunders, Philadelphia, PA

    Google Scholar 

  • Boron WF, Fong P, Hediger MA, Boulpaep EL, Romero MF (1997) The electrogenic Na/HCO3 cotransporter. Wien Klin Wochenschr 109(12–13):445–456

    CAS  PubMed  Google Scholar 

  • Bouzinova EV, Praetorius J, Virkki LV, Nielsen S, Boron WF, Aalkjaer C (2005) Na+− dependent HCO3 − uptake into the rat choroid plexus epithelium is partially DIDS sensitive. Am J Physiol Cell Physiol 289(6):C1448–C1456

    Article  CAS  PubMed  Google Scholar 

  • Burnham CE, Amlal H, Wang Z, Shull GE, Soleimani M (1997) Cloning and functional expression of a human kidney Na+:HCO3 − cotransporter. J Biol Chem 272(31):19111–19114

    Article  CAS  PubMed  Google Scholar 

  • Chang M-H, DiPiero JM, Sönnichsen FD, Romero MF (2008) Entry to “HCO3 tunnel” revealed by human mutation and structural model. J Biol Chem 283(26):18402–18410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Charoenphandhu N, Laohapitakworn S, Kraidith K, Nakkrasae LI, Jongwattanapisan P, Tharabenjasin P, Krishnamra N (2011) Electrogenic Na/HCO3 co-transporter-1 is essential for the parathyroid hormone-stimulated intestinal HCO secretion. Biochem Biophys Res Commun 409(4):775–779

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Cann MJ, Litvin TN, Iourgenko V, Sinclair ML, Levin LR, Buck J (2000) Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor. Science 289(5479):625–628

    Article  CAS  PubMed  Google Scholar 

  • Chen LM, Kelly ML, Parker MD, Bouyer P, Gill HS, Felie JM, Davis BA, Boron WF (2008a) Expression and localization of Na-driven Cl−-HCO3 − exchanger (SLC4A8) in rodent CNS. Neuroscience 153(1):162–174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen LM, Kelly ML, Rojas JD, Parker MD, Gill HS, Davis BA, Boron WF (2008b) Use of a new polyclonal antibody to study the distribution and glycosylation of the sodium-coupled bicarbonate transporter NCBE in rodent brain. Neuroscience 151(2):374–385

    Article  CAS  PubMed  Google Scholar 

  • Chen A-P, Holmes H, Chang M-H, Carleton L, Romero MF (2014) Targeted NBCe1A deletion causes proximal RTA: whole nbce1 (sh_nbce1) KO vs. nbce1A KO mice. J Am Soc Nephrol 25:71A

    Google Scholar 

  • Chinigarzadeh A, Kasim NF, Muniandy S, Kassim NM, Salleh N (2014) Genistein induces increase in fluid pH, Na+ and HCO3 − concentration, SLC26A6 and SLC4A4 (NBCe1)-B expression in the uteri of ovariectomized rats. Int J Mol Sci 15(1):958–976

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Choi I, Romero MF, Khandoudi N, Bril A, Boron WF (1999) Cloning and characterization of an electrogenic Na/HCO3 cotransporter from human heart. Am J Physiol 274(3 Pt 1):C576–C584

    Google Scholar 

  • Cooper GJ, Zhou Y, Bouyer P, Grichtchenko II, Boron WF (2002) Transport of volatile solutes through AQP1. J Physiol 542(Pt 1):17–29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Damkier HH, Nielsen S, Praetorius J (2007) Molecular expression of SLC4 derived Na+ dependent anion transporters in selected human tissues. Am J Physiol Regul Integr Comp Physiol 293(5):R2136–R2146

    Article  CAS  PubMed  Google Scholar 

  • De Lisle RC, Hopfer U (1986) Electrolyte permeabilities of pancreatic zymogen granules: implications for pancreatic secretion. Am J Physiol 250(4 Pt 1):G489–G496

    PubMed  Google Scholar 

  • Deda G, Ekim M, Guven A, Karagol U, Tumer N (2001) Hypopotassemic paralysis: a rare presentation of proximal renal tubular acidosis. J Child Neurol 16(10):770–771

    Article  CAS  PubMed  Google Scholar 

  • Demirci FY, Chang M-H, Mah TS, Romero MF, Gorin MB (2006) Proximal renal tubular acidosis and ocular pathology: L522P, a novel missense mutation in the gene (SLC4A4) for Sodium Bicarbonate Cotransporter protein (NBCe1). Mol Vis 12:324–330

    CAS  PubMed  Google Scholar 

  • Dinour D, Chang M-H, Satoh J-I, Smith BL, Angle N, Knecht A, Serban I, Holtzman EJ, Romero MF (2004) A novel missense mutation in the sodium bicarbonate cotransporter (NBCe1/SLC4A4) causes proximal tubular acidosis and glaucoma through ion transport defects. J Biol Chem 279(50):52238–52246

    Article  CAS  PubMed  Google Scholar 

  • Dorfman R, Li W, Sun L, Lin F, Wang Y, Sandford A, Pare PD, McKay K, Kayserova H, Piskackova T et al (2009) Modifier gene study of meconium ileus in cystic fibrosis: statistical considerations and gene mapping results. Hum Genet 126(6):763–778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Douglas R, Xia Y, Schmitt BM, Bevensee MO, Biemesderfer D, Boron WF, Haddad GG (1998) Developmental and stress-induced profile of two CNS pH regulatory proteins: the Na/H exchanger and the Na/HCO3 cotransporter. Soc Neurosci Absrt 24:1605

    Google Scholar 

  • Douglas RM, Schmitt BM, Xia Y, Bevensee MO, Biemesderfer D, Boron WF, Haddad GG (2001) Sodium-hydrogen exchangers and sodium-bicarbonate co-transporters: ontogeny of protein expression in the rat brain. Neuroscience 102(1):217–228

    Article  CAS  PubMed  Google Scholar 

  • Ducoudret O, Diakov A, Mueller-Berger S, Romero MF, Boron WF, Frömter E (2001) The renal Na-HCO3-cotransporter expressed in Xenopus laevis oocytes: inhibition by tenidap and benzamil and effect of temperature on transport rate and stoichiometry. Pflugers Arch 442(5):709–717

    Article  CAS  PubMed  Google Scholar 

  • Fukuda H, Hirata T, Nakamura N, Kawahara K, Wakabayashi S, Romero MF, Hirose S (2013) Na+/HCO3 cotransporter 4 (NBC4) is predominantly expressed in choroid plexus and involved in cerebrospinal fluid production. Biochem J 450:179–187

    Article  CAS  PubMed  Google Scholar 

  • Galeza-Kulik M, Zebracka J, Szpak-Ulczok S, Czarniecka AK, Kukulska A, Gubala E, Stojcev Z, Wiench M (2006) Expression of selected genes involved in transport of ions in papillary thyroid carcinoma. Endokrynologia Polska 57(Suppl A):26–31

    PubMed  Google Scholar 

  • Gasser KW, DiDomenico J, Hopfer U (1988a) Potassium transport by pancreatic and parotid zymogen granule membranes. Am J Physiol 255(6 Pt 1):C705–C711

    CAS  PubMed  Google Scholar 

  • Gasser KW, DiDomenico J, Hopfer U (1988b) Secretagogues activate chloride transport pathways in pancreatic zymogen granules. Am J Physiol 254(1 Pt 1):G93–G99

    CAS  PubMed  Google Scholar 

  • Gawenis LR, Bradford EM, Prasad V, Lorenz JN, Simpson JE, Clarke LL, Woo AL, Grisham C, Sanford LP, Doetschman T et al (2007) Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3 − cotransporter. J Biol Chem 282(12):9042–9052

    Article  CAS  PubMed  Google Scholar 

  • Gholami K, Muniandy S, Salleh N (2014) Modulation of sodium-bicarbonate co-transporter (SLC4A4/NBCe1) protein and mRNA expression in rat's uteri by sex-steroids and at different phases of the oestrous cycle. Res Vet Sci 96(1):164–170

    Article  CAS  PubMed  Google Scholar 

  • Giebisch G, Windhager E (2003) Transport of acids and bases. In: Boron WF, Boulpaep EL (eds) Medical physiology. Saunders, Philadelphia, PA

    Google Scholar 

  • Gregorio SF, Carvalho ES, Campinho MA, Power DM, Canario AV, Fuentes J (2014) Endocrine regulation of carbonate precipitate formation in marine fish intestine by stanniocalcin and PTHrP. J Exp Biol 217(Pt 9):1555–1562

    Article  PubMed  Google Scholar 

  • Grichtchenko II, Romero MF, Boron WF (2000) Extracellular HCO3 dependence of electrogenic Na/HCO3 cotransporters (NBC) cloned from salamander and rat kidney. J Gen Physiol 115(5):533–546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gross E, Hopfer U (1999) Effects of pH on kinetic parameters of the Na-HCO3 cotransporter in renal proximal tubule. Biophys J 76(6):3066–3075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gross E, Hawkins K, Abuladze N, Pushkin A, Cotton CU, Hopfer U, Kurtz I (2001a) The stoichiometry of the electrogenic sodium bicarbonate cotransporter NBC1 is cell-type dependent. J Physiol 531(3):597–603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gross E, Hawkins K, Pushkin A, Sassani P, Dukkipati R, Abuladze N, Hopfer U, Kurtz I (2001b) Phosphorylation of Ser(982) in the sodium bicarbonate cotransporter kNBC1 shifts the HCO(3)(−): Na(+) stoichiometry from 3: 1 to 2: 1 in murine proximal tubule cells. J Physiol 537(Pt 3):659–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gross E, Fedotoff O, Pushkin A, Abuladze N, Newman D, Kurtz I (2003) Phosphorylation-induced modulation of pNBC1 function: distinct roles for the amino- and carboxy-termini. J Physiol 549(Pt 3):673–682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heyer M, Müller-Berger S, Romero MF, Boron WF, Frömter E (1999) Stoichiometry of rat kidney Na-HCO3 cotransporter (rkNBC) expressed in Xenopus laevis oocytes. Pflugers Arch 438(3):322–329

    Article  CAS  PubMed  Google Scholar 

  • Hihnala S, Kujala M, Toppari J, Kere J, Holmberg C, Hoglund P (2006) Expression of SLC26A3, CFTR and NHE3 in the human male reproductive tract: role in male subfertility caused by congenital chloride diarrhoea. Mol Hum Reprod 12(2):107–111

    Article  CAS  PubMed  Google Scholar 

  • Hirata T, Kaneko T, Ono T, Nakazato T, Furukawa N, Hasegawa S, Wakabayashi S, Shigekawa M, Chang M-H, Romero MF et al (2003) Mechanism of acid adaptation of a fish living in a pH 3.5 lake. Am J Physiol Regul Integr Comp Physiol 284(5):R1199–R1212

    Article  CAS  PubMed  Google Scholar 

  • Hong JH, Yang D, Shcheynikov N, Ohana E, Shin DM, Muallem S (2013) Convergence of IRBIT, phosphatidylinositol (4,5) bisphosphate, and WNK/SPAK kinases in regulation of the Na+−HCO3 − cotransporters family. Proc Natl Acad Sci USA 110(10):4105–4110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Horita S, Yamada H, Inatomi J, Moriyama N, Sekine T, Igarashi T, Endo Y, Dasouki M, Ekim M, Al-Gazali L et al (2005) Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities. J Am Soc Nephrol 16(8):2270–8

    Article  CAS  PubMed  Google Scholar 

  • Igarashi T, Inatomi J, Sekine T, Cha SH, Kanai Y, Kunimi M, Tsukamoto K, Satoh H, Shimadzu M, Tozawa F et al (1999) Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities. Nat Genet 23(3):264–266

    Article  CAS  PubMed  Google Scholar 

  • Igarashi T, Inatomi J, Sekine T, Seki G, Shimadzu M, Tozawa F, Takeshima Y, Takumi T, Takahashi T, Yoshikawa N et al (2001) Novel nonsense mutation in the Na+/HCO3 − cotransporter gene (SLC4A4) in a patient with permanent isolated proximal renal tubular acidosis and bilateral glaucoma. J Am Soc Nephrol 12(4):713–718

    CAS  PubMed  Google Scholar 

  • Igarashi T, Sekine T, Inatomi J, Seki G (2002) Unraveling the molecular pathogenesis of isolated proximal renal tubular acidosis. J Am Soc Nephrol 13(8):2171–2177

    Article  PubMed  Google Scholar 

  • Igarashi T, Inatomi J, Sekine T, Seki G, Yamada H, Horita S, Fujita T (2003) Mutational and functional analysis of the Na+/HCO3 − cotransporter gene (SLC4A4) in patients with permanent isolated proximal renal tubular acidosis and ocular abnormalities. J Am Soc Nephrol 14(Suppl S):302A–302A

    Google Scholar 

  • Ishiguro H, Naruse S, Steward MC, Kitagawa M, Ko SB, Hayakawa T, Case RM (1998) Fluid secretion in interlobular ducts isolated from guinea-pig pancreas. J Physiol Lond 511(Pt 2):407–422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jacob P, Christiani S, Rossmann H, Lamprecht G, Vieillard-Baron D, Muller R, Gregor M, Seidler U (2000) Role of Na+/HCO3 − cotransporter NBC1, Na+/H+ exchanger NHE1, and carbonic anhydrase in rabbit duodenal bicarbonate secretion. Gastroenterology 119(2):406–419

    Article  CAS  PubMed  Google Scholar 

  • Jakab RL, Collaco AM, Ameen NA (2011) Physiological relevance of cell-specific distribution patterns of CFTR, NKCC1, NBCe1, and NHE3 along the crypt-villus axis in the intestine. Am J Physiol Gastrointest Liver Physiol 300(1):G82–G98

    Article  CAS  PubMed  Google Scholar 

  • Jalali R, Guo J, Zandieh-Doulabi B, Bervoets TJ, Paine ML, Boron WF, Parker MD, Bijvelds MJ, Medina JF, DenBesten PK et al (2014) NBCe1 (SLC4A4) a potential pH regulator in enamel organ cells during enamel development in the mouse. Cell Tissue Res 358(2):433–442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jensen LJ, Schmitt BM, Berger UV, Nsumu NN, Boron WF, Hediger MA, Brown D, Breton S (1999) Localization of sodium bicarbonate cotransporter (NBC) protein and messenger ribonucleic acid in rat epididymis. Biol Reprod 60(3):573–579

    Article  CAS  PubMed  Google Scholar 

  • Jentsch TJ, Schill BS, Schwartz P, Matthes H, Keller SK, Wiederholt M (1985) Kidney epithelial cells of monkey origin (BSC-1) express a sodium bicarbonate cotransport. Characterization by 22Na+ flux measurements. J Biol Chem 260(29):15554–15560

    CAS  PubMed  Google Scholar 

  • Joseph A, Hess RA, Schaeffer DJ, Ko C, Hudgin-Spivey S, Chambon P, Shur BD (2010) Absence of estrogen receptor alpha leads to physiological alterations in the mouse epididymis and consequent defects in sperm function. Biol Reprod 82(5):948–957

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kao L, Kurtz LM, Shao X, Papadopoulos MC, Liu L, Bok D, Nusinowitz S, Chen B, Stella SL, Andre M et al (2011) Severe neurologic impairment in mice with targeted disruption of the electrogenic sodium bicarbonate cotransporter NBCe2 (Slc4a5 gene). J Biol Chem 286(37):32563–32574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khandoudi N, Albadine J, Robert P, Krief S, Berrebi-Bertrand I, Martin X, Bevensee MO, Boron WF, Bril A (2001) Inhibition of the cardiac electrogenic sodium bicarbonate cotransporter reduces ischemic injury. Cardiovasc Res 52(3):387–396

    Article  CAS  PubMed  Google Scholar 

  • Kleinboelting S, Diaz A, Moniot S, van den Heuvel J, Weyand M, Levin LR, Buck J, Steegborn C (2014) Crystal structures of human soluble adenylyl cyclase reveal mechanisms of catalysis and of its activation through bicarbonate. Proc Natl Acad Sci USA 111(10):3727–3732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ko SB, Shcheynikov N, Choi JY, Luo X, Ishibashi K, Thomas PJ, Kim JY, Kim KH, Lee MG, Naruse S et al (2002) A molecular mechanism for aberrant CFTR-dependent HCO3 − transport in cystic fibrosis. EMBO J 21(21):5662–5672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ko SB, Zeng W, Dorwart MR, Luo X, Kim KH, Millen L, Goto H, Naruse S, Soyombo A, Thomas PJ et al (2004) Gating of CFTR by the STAS domain of SLC26 transporters. Nat Cell Biol 6(4):343–350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Konturek SJ, Konturek PC, Pawlik T, Sliwowski Z, Ochmanski W, Hahn EG (2004) Duodenal mucosal protection by bicarbonate secretion and its mechanisms. J Physiol Pharmacol 55(Suppl 2):5–17

    PubMed  Google Scholar 

  • Koo NY, Li J, Hwang SM, Choi SY, Lee SJ, Oh SB, Kim JS, Lee JH, Park K (2006) Molecular cloning and functional expression of a sodium bicarbonate cotransporter from guinea-pig parotid glands. Biochem Biophys Res Commun 342(4):1114–1122

    Article  CAS  PubMed  Google Scholar 

  • Kreindler JL, Peters KW, Frizzell RA, Bridges RJ (2006) Identification and membrane localization of electrogenic sodium bicarbonate cotransporters in Calu-3 cells. Biochim Biophys Acta 1762(7):704–710

    Article  CAS  PubMed  Google Scholar 

  • Kurita Y, Nakada T, Kato A, Doi H, Mistry AC, Chang M-H, Romero MF, Hirose S (2008a) Identification of intestinal bicarbonate transporters involved in formation of carbonate precipitates to stimulate water absorption in marine teleost fish. FASEB J 22 (PMID EB-abstract)

    Google Scholar 

  • Kurita Y, Nakada T, Kato A, Mistry AC, Chang M-H, Romero MF, Hirose S (2008b) Identification of intestinal bicarbonate transporters involved in formation of carbonate precipitates to stimulate water absorption in marine teleost fish. Am J Physiol Regul Integr Comp Physiol 284(4):R1402–R1412

    Article  CAS  Google Scholar 

  • Kurtz I, Zhu Q (2013) Proximal renal tubular acidosis mediated by mutations in NBCe1-A: unraveling the transporter’s structure-functional properties. Front Physiol 4:350

    Article  PubMed  PubMed Central  Google Scholar 

  • Lacruz RS, Nanci A, White SN, Wen X, Wang H, Zalzal SF, Luong VQ, Schuetter VL, Conti PS, Kurtz I et al (2010) The sodium bicarbonate cotransporter (NBCe1) is essential for normal development of mouse dentition. J Biol Chem 285(32):24432–24438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee SH, Park JH, Jung HH, Oh JW, Lee HM, Jun HS, Cho WJ, Lee JY (2005) Expression and distribution of ion transport mRNAs in human nasal mucosa and nasal polyps. Acta Otolaryngol 125(7):745–752

    Article  PubMed  CAS  Google Scholar 

  • Lee MG, Ohana E, Park HW, Yang D, Muallem S (2012a) Molecular mechanism of pancreatic and salivary gland fluid and HCO3 secretion. Physiol Rev 92(1):39–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee SK, Boron WF, Parker MD (2012b) Relief of autoinhibition of the electrogenic Na-HCO3 cotransporter NBCe1-B: role of IRBIT vs.amino-terminal truncation. Am J Physiol Cell Physiol 302(3):C518–C526

    Article  CAS  PubMed  Google Scholar 

  • Lee SK, Boron WF, Parker MD (2013) Substrate specificity of the electrogenic sodium/bicarbonate cotransporter NBCe1-A (SLC4A4, variant A) from humans and rabbits. Am J Physiol Renal Physiol 304(7):F883–F899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li HC, Worrell RT, Matthews JB, Husseinzadeh H, Neumeier L, Petrovic S, Conforti L, Soleimani M (2004) Identification of a carboxyl-terminal motif essential for the targeting of Na+/HCO3 − cotransporter NBC1 to the basolateral membrane. J Biol Chem 279(41):43190–43197

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Xu JY, Wang DK, Wang L, Chen LM (2011) Cloning and identification of two novel NBCe1 splice variants from mouse reproductive tract tissues: a comparative study of NCBT genes. Genomics 98(2):112–119

    Article  CAS  PubMed  Google Scholar 

  • Lo YF, Yang SS, Seki G, Yamada H, Horita S, Yamazaki O, Fujita T, Usui T, Tsai JD, Yu IS et al (2011) Severe metabolic acidosis causes early lethality in NBC1 W516X knock-in mice as a model of human isolated proximal renal tubular acidosis. Kidney Int Suppl 79(7):730–741

    Article  CAS  Google Scholar 

  • Lu J, Boron WF (2007) Reversible and irreversible interactions of DIDS with the human electrogenic Na/HCO3 cotransporter NBCe1-A: role of lysines in the KKMIK motif of TM5. Am J Physiol Cell Physiol 292(5):C1787–C1798

    Article  CAS  PubMed  Google Scholar 

  • Luo X, Choi JY, Ko SB, Pushkin A, Kurtz I, Ahn W, Lee MG, Muallem S (2001) HCO3 − salvage mechanisms in the submandibular gland acinar and duct cells. J Biol Chem 3:3

    Google Scholar 

  • Majumdar D, Maunsbach AB, Shacka JJ, Williams JB, Berger UV, Schultz KP, Harkins LE, Boron WF, Roth KA, Bevensee MO (2008) Localization of electrogenic Na/bicarbonate cotransporter NBCe1 variants in rat brain. Neuroscience 155(3):818–832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marino CR, Jeanes V, Boron WF, Schmitt BM (1999) Expression and distribution of the Na+-HCO3 − cotransporter in human pancreas. Am J Physiol 277(2 Pt 1):G487–G494

    CAS  PubMed  Google Scholar 

  • Maunsbach AB, Vorum H, Kwon TH, Nielsen S, Simonsen B, Choi I, Schmitt BM, Boron WF, Aalkjaer C (2000) Immunoelectron microscopic localization of the electrogenic Na/HCO3 cotransporter in rat and ambystoma kidney. J Am Soc Nephrol 11(12):2179–2189

    CAS  PubMed  Google Scholar 

  • McAlear SD, Liu X, Williams JB, McNicholas-Bevensee CM, Bevensee MO (2006) Electrogenic Na/HCO3 cotransporter (NBCe1) variants expressed in Xenopus oocytes: functional comparison and roles of the amino and carboxy termini. J Gen Physiol 127(6):639–658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moss F, Lee S, Parker M, Boron W (2014) Distinguishing HCO3 − from CO3 = transport by the electrogenic Na/HCO3 cotransporter NBCe1 (SLC4A4). FASEB J 28(1):a1098.7

    Google Scholar 

  • Muller-Berger S, Ducoudret O, Diakov A, Fromter E (2001) The renal Na-HCO3-cotransporter expressed in Xenopus laevis oocytes: change in stoichiometry in response to elevation of cytosolic Ca2+ concentration. Pflugers Arch 442(5):718–728

    Article  CAS  PubMed  Google Scholar 

  • Musa-Aziz R, Chen LM, Pelletier MF, Boron WF (2009) Relative CO2 / NH3 selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG. Proc Natl Acad Sci USA 106(13):5406–5411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Myers E, Yuan L, Felmlee M, Lin YY, Jiang Y, Pei Y, Wang O, Li M, Xing XP, Marshall A et al (2015) A novel missense mutation in the NBCe1 gene (SLC4A4) and a novel mode of inheritance for proximal renal tubular acidosis (pRTA). FASEB J 29(1 Supp):809.24, abstract

    Google Scholar 

  • Nakhoul NL, Davis BA, Romero MF, Boron WF (1998) Effect of expressing the water channel aquaporin-1 on the CO2 permeability of Xenopus oocytes [see comments]. Am J Physiol 274(2 Pt 1):C543–C548

    CAS  PubMed  Google Scholar 

  • Newman EA, Astion ML (1991) Localization and stoichiometry of electrogenic sodium bicarbonate cotransport in retinal glial cells. Glia 4(4):424–428

    Article  CAS  PubMed  Google Scholar 

  • Orlowski A, Ciancio MC, Caldiz CI, De Giusti VC, Aiello EA (2014) Reduced sarcolemmal expression and function of the NBCe1 isoform of the Na+-HCO3 − cotransporter in hypertrophied cardiomyocytes of spontaneously hypertensive rats: role of the renin-angiotensin system. Cardiovasc Res 101(2):211–219

    Article  CAS  PubMed  Google Scholar 

  • Paine ML, Snead ML, Wang HJ, Abuladze N, Pushkin A, Liu W, Kao LY, Wall SM, Kim YH, Kurtz I (2008) Role of NBCe1 and AE2 in secretory ameloblasts. J Dent Res 87(4):391–395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park K, Hurley PT, Roussa E, Cooper GJ, Smith CP, Thevenod F, Steward MC, Case RM (2002) Expression of a sodium bicarbonate cotransporter in human parotid salivary glands. Arch Oral Biol 47(1):1–9

    Article  CAS  PubMed  Google Scholar 

  • Park S, Hong JH, Ohana E, Muallem S (2012) The WNK/SPAK and IRBIT/PP1 pathways in epithelial fluid and electrolyte transport. Physiology 27(5):291–299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parker MD, Boron WF (2013) The divergence, actions, roles, and relatives of sodium-coupled bicarbonate transporters. Physiol Rev 93(2):803–959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pastor-Soler N, Beaulieu V, Litvin TN, Da Silva N, Chen Y, Brown D, Buck J, Levin LR, Breton S (2003) Bicarbonate-regulated adenylyl cyclase (sAC) is a sensor that regulates pH-dependent V-ATPase recycling. J Biol Chem 278(49):49523–49529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pastor-Soler N, Pietrement C, Breton S (2005) Role of acid/base transporters in the male reproductive tract and potential consequences of their malfunction. Physiology 20:417–428

    Article  CAS  PubMed  Google Scholar 

  • Perry C, Blaine J, Le H, Grichtchenko II (2006) PMA- and ANG II-induced PKC regulation of the renal Na+-HCO3 − cotransporter (hkNBCe1). Am J Physiol Renal Physiol 290(2):F417–F427

    Article  CAS  PubMed  Google Scholar 

  • Perry C, Le H, Grichtchenko II (2007) ANG II and calmodulin/CaMKII regulate surface expression and functional activity of NBCe1 via separate means. Am J Physiol Renal Physiol 293(1):F68–F77

    Article  CAS  PubMed  Google Scholar 

  • Perry C, Baker OJ, Reyland ME, Grichtchenko II (2009) PKCαβγ- and PKCδ dependent endocytosis of NBCe1-A and NBCe1-B in salivary parotid acinar cells. Am J Physiol Cell Physiol 297(6):C1409–C1423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Piermarini PM, Choi I, Boron WF (2007) Cloning and characterization of an electrogenic Na/HCO3 − cotransporter from the squid giant fiber lobe. Am J Physiol Cell Physiol 292(6):C2032–C2045

    Article  CAS  PubMed  Google Scholar 

  • Praetorius J, Hager H, Nielsen S, Aalkjaer C, Friis UG, Ainsworth MA, Johansen T (2001) Molecular and functional evidence for electrogenic and electroneutral Na+-HCO3 − cotransporters in murine duodenum. Am J Physiol Gastrointest Liver Physiol 280(3):G332–G343

    CAS  PubMed  Google Scholar 

  • Prasad GVR, Coury LA, Finn F, Zeidel ML (1998) Reconstituted aquaporin 1 water channels transport CO2 across membranes. J Biol Chem 273(50):33123–33126

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez-Martinez H, Ekstedt E, Einarsson S (1990) Acidification of epididymal fluid in the boar. Int J Androl 13(3):238–243

    Article  CAS  PubMed  Google Scholar 

  • Romero MF (2001) The electrogenic Na+/HCO3 − cotransporter, NBC. JOP 2(4 Suppl):182–191

    CAS  PubMed  Google Scholar 

  • Romero MF, Boron WF (1999) Electrogenic Na/HCO3 cotransporters: expression cloning and physiology. Ann Rev Physiol 61:699–723

    Article  CAS  Google Scholar 

  • Romero MF, Hediger MA, Boulpaep EL, Boron WF (1997) Expression cloning and characterization of a renal electrogenic Na+/HCO3 − cotransporter. Nature 387(6631):409–413

    Article  CAS  PubMed  Google Scholar 

  • Romero MF, Davis BA, Sussman CR, Bray-Ward P, Ward D, Boron WF (1998a) Identification of multiple genes for human electrogenic Na/HCO3 cotransporters (NBC) on 4q. J Am Soc Nephrol 9:11A

    Google Scholar 

  • Romero MF, Fong P, Berger UV, Hediger MA, Boron WF (1998b) Cloning and functional expression of rNBC, an electrogenic Na+-HCO3 − cotransporter from rat kidney. Am J Physiol 274(2 Pt 2):F425–F432

    CAS  PubMed  Google Scholar 

  • Romero MF, Fulton CM, Boron WF (2004) The SLC4 gene family of HCO3 − transporters. Pflugers Arch 447(5):495–509

    Article  CAS  PubMed  Google Scholar 

  • Romero MF, Chen AP, Parker MD, Boron WF (2013a) The SLC4 family of bicarbonate (HCO3 −) transporters. Mol Asp Med 34(2–3):159–182

    Article  CAS  Google Scholar 

  • Romero MF, Holmes HL, Chowdhury UR, Hann CR, Chang M-H, Fautsch MP, Chen A-P (2013b) Ocular indications of partial penetrance in mice heterozygous for NBCe1 (Slc4a4). Invest Ophthalmol Vis Sci 54(15):5646, abstract

    Google Scholar 

  • Romero MF, Holmes HL, Chowdhury UR, Hann CR, Chang M-H, Fautsch MP, Chen A-P (2014) Mutants in NBCe1A isoform have elevated intraocular pressure. Invest Ophthalmol Vis Sci 55: 2415, abstract

    Google Scholar 

  • Rossmann H, Bachmann O, Vieillard-Baron D, Gregor M, Seidler U (1999) Na+/HCO3 − cotransport and expression of NBC1 and NBC2 in rabbit gastric parietal and mucous cells. Gastroenterology 116(6):1389–1398

    Article  CAS  PubMed  Google Scholar 

  • Roussa E, Romero MF, Schmitt BM, Boron WF, Alper SL, Thévenod F (1999) Immunolocalization of AE2 anion exchanger and Na+-HCO3 − cotransporter in rat parotid and submandibular glands. Am J Physiol 277(6 Pt 1):G1288–G1296

    CAS  PubMed  Google Scholar 

  • Ruminot I, Gutierrez R, Pena-Munzenmayer G, Anazco C, Sotelo-Hitschfeld T, Lerchundi R, Niemeyer MI, Shull GE, Barros LF (2011) NBCe1 mediates the acute stimulation of astrocytic glycolysis by extracellular K+. J Neurosci 31(40):14264–14271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmitt BM, Berger UV, Douglas RM, Bevensee MO, Hediger MA, Haddad GG, Boron WF (2000) Na/HCO3 cotransporters in rat brain: expression in glia, neurons, and choroid plexus. J Neurosci 20(18):6839–6848

    CAS  PubMed  Google Scholar 

  • Schueler C, Becker HM, McKenna R, Deitmer JW (2011) Transport activity of the sodium bicarbonate cotransporter NBCe1 Is enhanced by different isoforms of carbonic anhydrase. PLoS ONE 6(11), e27167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sciortino CM, Romero MF (1999) Cation and voltage dependence of rat kidney, electrogenic Na/HCO cotransporter, rkNBC, expressed in oocytes. Am J Physiol 277(4 Pt 2):F611–F623

    CAS  PubMed  Google Scholar 

  • Seidler U, Bachmann O, Jacob P, Christiani S, Blumenstein I, Rossmann H (2001) Na+/HCO3 − cotransport in normal and cystic fibrosis intestine. JOP 2(4 Suppl):247–256

    CAS  PubMed  Google Scholar 

  • Sergeev M, Godin AG, Kao L, Abuladze N, Wiseman PW, Kurtz I (2012) Determination of membrane protein transporter oligomerization in native tissue using spatial fluorescence intensity fluctuation analysis. PLoS ONE 7(4), e36215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shirakabe K, Priori G, Yamada H, Ando H, Horita S, Fujita T, Fujimoto I, Mizutani A, Seki G, Mikoshiba K (2006) 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 USA 103(25):9542–9547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shnitsar V, Li J, Li X, Calmettes C, Basu A, Casey JR, Moraes TF, Reithmeier RA (2013) A substrate access tunnel in the cytosolic domain is not an essential feature of the solute carrier 4 (SLC4) family of bicarbonate transporters. J Biol Chem 288(47):33848–33860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sinclair ML, Wang XY, Mattia M, Conti M, Buck J, Wolgemuth DJ, Levin LR (2000) Specific expression of soluble adenylyl cyclase in male germ cells. Mol Reprod Dev 56(1):6–11

    Article  CAS  PubMed  Google Scholar 

  • Sinđić A, Sussman CR, Romero MF (2010) Primers on molecular pathways - bicarbonate transport by the pancreas. Pancreatology 10(6):660–663

    Article  PubMed  CAS  Google Scholar 

  • Skelton LA, Boron WF, Zhou Y (2010) Acid–base transport by the renal proximal tubule. J Nephrol 23(Suppl 16):S4–S18

    PubMed  PubMed Central  Google Scholar 

  • Soleimani M, Aronson PS (1989) Ionic mechanism of Na+-HCO3 − cotransport in rabbit renal basolateral membrane vesicles. J Biol Chem 264(31):18302–18308

    CAS  PubMed  Google Scholar 

  • Soleimani M, Lesoine GA, Bergman JA, Aronson PS (1991) Cation specificity and modes of the Na+:CO3 2−:HCO3 − cotransporter in renal basolateral membrane vesicles. J Biol Chem 266(14):8706–8710

    CAS  PubMed  Google Scholar 

  • Soleimani M, Hattabaugh YJ, Bizal GL (1992) pH sensitivity of the Na+:HCO3 − cotransporter in basolateral membrane vesicles isolated from rabbit kidney cortex. J Biol Chem 267(26):18349–18355

    CAS  PubMed  Google Scholar 

  • Soyfoo MS, Bulur N, Virreira M, Louchami K, Lybaert P, Crutzen R, Perret J, Delporte C, Roussa E, Thevenod F et al (2009) Expression of the electrogenic Na+-HCO3 −-cotransporters NBCe1-A and NBCe1-B in rat pancreatic islet cells. Endocrine 35(3):449–458

    Article  CAS  PubMed  Google Scholar 

  • Steward MC, Ishiguro H, Case RM (2005) Mechanisms of bicarbonate secretion in the pancreatic duct. Annu Rev Physiol 67:377–409

    Article  CAS  PubMed  Google Scholar 

  • Sun XC, Bonanno JA (2003) Identification and cloning of the Na/HCO3 − cotransporter (NBC) in human corneal endothelium. Exp Eye Res 77(3):287–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki M, Vaisbich MH, Yamada H, Horita S, Li Y, Sekine T, Moriyama N, Igarashi T, Endo Y, Cardoso TP et al (2008) Functional analysis of a novel missense NBC1 mutation and of other mutations causing proximal renal tubular acidosis. Pflugers Arch 455(4):583–593

    Article  CAS  PubMed  Google Scholar 

  • Suzuki M, Van Paesschen W, Stalmans I, Horita S, Yamada H, Bergmans BA, Legius E, Riant F, De Jonghe P, Li Y et al (2010) Defective membrane expression of the Na+-HCO3 − cotransporter NBCe1 is associated with familial migraine. Proc Natl Acad Sci USA 107(36):15963–15968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tajima Y, Okamura N, Sugita Y (1987) The activating effects of bicarbonate on sperm motility and respiration at ejaculation. Biochim Biophys Acta 924(3):519–529

    Article  CAS  PubMed  Google Scholar 

  • Ten Hove M, Nederhoff MG, Van Echteld CJ (2004) Relative contributions of Na+/H+ exchange and Na+/HCO3 − co-transport to ischemic Na+ i overload in isolated rat hearts. Am J Physiol Heart Circ Physiol 288(1):H287–H292

    Article  PubMed  CAS  Google Scholar 

  • Thevenod F, Gasser KW, Hopfer U (1990) Dual modulation of chloride conductance by nucleotides in pancreatic and parotid zymogen granules. Biochem J 272(1):119–126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thevenod F, Chathadi KV, Jiang B, Hopfer U (1992) ATP-sensitive K+ conductance in pancreatic zymogen granules: block by glyburide and activation by diazoxide. J Membr Biol 129(3):253–266

    Article  CAS  PubMed  Google Scholar 

  • Thévenod F, Roussa E, Schmitt BM, Romero MF (1999) Cloning and immunolocalization of a rat pancreatic Na+ bicarbonate cotransporter. Biochem Biophys Res Commun 264(1):291–298

    Article  PubMed  Google Scholar 

  • Toye AM, Parker MD, Daly CM, Lu J, Virkki LV, Pelletier MF, Boron WF (2006) The human NBCe1-A mutant R881C, associated with proximal renal tubular acidosis, retains function but is mistargeted in polarized renal epithelia. Am J Physiol Cell Physiol 291(4):C788–C801

    Article  CAS  PubMed  Google Scholar 

  • Turner HC, Alvarez LJ, Candia OA (2001) Identification and localization of acid–base transporters in the conjunctival epithelium. Exp Eye Res 72(5):519–531

    Article  CAS  PubMed  Google Scholar 

  • Usui T, Hara M, Satoh H, Moriyama N, Kagaya H, Amano S, Oshika T, Ishii Y, Ibaraki N, Hara C et al (2001) Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis. J Clin Invest 108(1):107–115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang HS, Chen Y, Vairamani K, Shull GE (2014) Critical role of bicarbonate and bicarbonate transporters in cardiac function. World J Biol Chem 5(3):334–345

    Article  PubMed  PubMed Central  Google Scholar 

  • Wen X, Kurtz I, Paine ML (2014) Prevention of the disrupted enamel phenotype in Slc4a4-null mice using explant organ culture maintained in a living host kidney capsule. PLoS ONE 9(5), e97318

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu J, McNicholas CM, Bevensee MO (2009) Phosphatidylinositol 4,5-bisphosphate (PIP2) stimulates the electrogenic Na/HCO3 cotransporter NBCe1-A expressed in Xenopus oocytes. Proc Natl Acad Sci USA 106(33):14150–14155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xue H, Tian YM, Yan M, Yang N, Chen X, Xing Y, Zhu JX (2007) Appearance of segmental discrepancy of anion transport in rat distal colon. Biol Pharm Bull 30(8):1407–1411

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto T, Shirayama T, Sakatani T, Takahashi T, Tanaka H, Takamatsu T, Spitzer KW, Matsubara H (2007) Enhanced activity of ventricular Na+-HCO3 − cotransport in pressure overload hypertrophy. Am J Physiol Heart Circ Physiol 293(2):H1254–H1264

    Article  CAS  PubMed  Google Scholar 

  • Yamazaki O, Yamada H, Suzuki M, Horita S, Shirai A, Nakamura M, Satoh N, Fujita T, Seki G (2013) Identification of dominant negative effect of L522P mutation in the electrogenic Na+-HCO3 − cotransporter NBCe1. Pflugers Arch 465(9):1281–1291

    Article  CAS  PubMed  Google Scholar 

  • Yang D, Shcheynikov N, Zeng W, Ohana E, So I, Ando H, Mizutani A, Mikoshiba K, Muallem S (2009a) IRBIT coordinates epithelial fluid and HCO3 − secretion by stimulating the transporters pNBC1 and CFTR in the murine pancreatic duct. J Clin Invest 119(1):193–202

    CAS  PubMed  Google Scholar 

  • Yang HS, Kim E, Lee S, Park HJ, Cooper DS, Rajbhandari I, Choi I (2009b) Mutation of aspartate 555 of the sodium/bicarbonate transporter SLC4A4/NBCe1 induces chloride transport. J Biol Chem 284(23):15970–15979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang D, Li Q, So I, Huang CL, Ando H, Mizutani A, Seki G, Mikoshiba K, Thomas PJ, Muallem S (2011) IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK kinase pathway. J Clin Invest 121(3):956–965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu H, Riederer B, Stieger N, Boron WF, Shull GE, Manns MP, Seidler UE, Bachmann O (2009) Secretagogue stimulation enhances NBCe1 (electrogenic Na+/HCO3 − cotransporter) surface expression in murine colonic crypts. Am J Physiol Gastrointest Liver Physiol 297(6):G1223–G1231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao WC, Duan DX, Wang ZJ, Tang N, Yan M, Zhang GH, Xing Y (2005) The underlying cellular mechanism in the effect of tetramethylpyrazine on the anion secretion of colonic mucosa. Jpn J Physiol 55(6):325–329

    Article  CAS  PubMed  Google Scholar 

  • Zheng L, Zhang Y, He P, Kim J, Schneider R, Bronckers AL, Lyaruu DM, DenBesten PK (2011) NBCe1 in mouse and human ameloblasts may be indirectly regulated by fluoride. J Dent Res 90(6):782–787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu Q, Kao L, Azimov R, Abuladze N, Newman D, Pushkin A, Liu W, Chang C, Kurtz I (2010a) Structural and functional characterization of the C-terminal transmembrane region of NBCe1-A. J Biol Chem 285(48):37178–37187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu Q, Kao L, Azimov R, Newman D, Liu W, Pushkin A, Abuladze N, Kurtz I (2010b) Topological location and structural importance of the NBCe1-A residues mutated in proximal renal tubular acidosis. J Biol Chem 285(18):13416–13426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu Q, Liu W, Kao L, Azimov R, Newman D, Abuladze N, Kurtz I (2013a) Topology of NBCe1 protein transmembrane segment 1 and structural effect of proximal renal tubular acidosis (pRTA) S427L mutation. J Biol Chem 288(11):7894–7906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu Q, Shao XM, Kao L, Azimov R, Weinstein AM, Newman D, Liu W, Kurtz I (2013b) Missense mutation T485S alters NBCe1-A electrogenicity causing proximal renal tubular acidosis. Am J Physiol Cell Physiol 305(4):C392–C405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zippin JH, Levin LR, Buck J (2001) CO2 / HCO3 −-responsive soluble adenylyl cyclase as a putative metabolic sensor. Trends Endocrinol Metab 12(8):366–370

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank our collaborators and past members of the Romero lab who contributed to some of the basic physiology. This work was supported by NIH EY017732 (MFR), the Cystic Fibrosis Foundation (Sindic-06F0, Romero-06G0), the Arlene and Robert Kogod Aging Center, and the Mayo Foundation.

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Authors and Affiliations

  1. Physiology and Immunology, School of Medicine, University of Zagreb, Šalata 3, 10000, Zagreb, Croatia

    Aleksandra Sinđić

  2. Physiology and Biomedical Engineering, Nephrology and Hypertension, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN, 55905, USA

    Michael F. Romero

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  1. Aleksandra Sinđić
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  2. Michael F. Romero
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Correspondence to Michael F. Romero .

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  1. Department of Physiology, University of Otago , Dunedin, Otago, New Zealand

    Kirk L. Hamilton

  2. Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Daniel C Devor

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Sinđić, A., Romero, M.F. (2016). NBCe1, an Electrogenic Na+ Bicarbonate Cotransporter, in Epithelia. In: Hamilton, K., Devor, D. (eds) Ion Channels and Transporters of Epithelia in Health and Disease. Physiology in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3366-2_13

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