title: Distribution of transcellular calcium and sodium transport pathways along mouse distal nephron.
abstract: The organization of Na(+) and Ca(2+) transport pathways along the mouse distal nephron is incompletely known. We revealed by immunohistochemistry a set of Ca(2+) and Na(+) transport proteins along the mouse distal convolution. The thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC) characterized the distal convoluted tubule (DCT). The amiloride-sensitive epithelial Na(+) channel (ENaC) colocalized with NCC in late DCT (DCT2) and extended to the downstream connecting tubule (CNT) and collecting duct (CD). In early DCT (DCT1), the basolateral Ca(2+)-extruding proteins [Na(+)/Ca(2+) exchanger (NCX), plasma membrane Ca(2+)-ATPase (PCMA)] and the cytoplasmic Ca(2+)-binding protein calbindin D(28K) (CB) were found at very low levels, whereas the cytoplasmic Ca(2+)/Mg(2+)-binding protein parvalbumin was highly abundant. NCX, PMCA, and CB prevailed in DCT2 and CNT, where we located the apical epithelial Ca(2+) channel (ECaC1). Its subcellular localization changed from apical in DCT2 to exclusively cytoplasmic at the end of CNT. NCX and PMCA decreased in parallel with the fading of ECaC1 in the apical membrane. All three of them were undetectable in CD. These findings disclose DCT2 and CNT as major sites for transcellular Ca(2+) transport in the mouse distal nephron. Cellular colocalization of Ca(2+) and Na(+) transport pathways suggests their mutual interactions in transport regulation.
authors.affiliation: Institute of Anatomy, University of Zurich, CH-8057 Zurich. jloffing@anatom.unizh.ch
authors.forename: J
authors.initials: J
authors.lastname: Loffing
authors.forename: D
authors.initials: D
authors.lastname: Loffing-Cueni
authors.forename: V
authors.initials: V
authors.lastname: Valderrabano
authors.forename: L
authors.initials: L
authors.lastname: Kläusli
authors.forename: S C
authors.initials: SC
authors.lastname: Hebert
authors.forename: B C
authors.initials: BC
authors.lastname: Rossier
authors.forename: J G
authors.initials: JG
authors.lastname: Hoenderop
authors.forename: R J
authors.initials: RJ
authors.lastname: Bindels
authors.forename: B
authors.initials: B
authors.lastname: Kaissling
mesh_terms: D000818:Animals; D064026:Calbindins; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000032:analysis / Q000276:immunology; D000252:Calcium-Transporting ATPases / Q000032:analysis / Q000276:immunology; D002352:Carrier Proteins / Q000032:analysis* / Q000276:immunology; D027682:Cation Transport Proteins; D053503:Epithelial Sodium Channels; D005260:Female; D007150:Immunohistochemistry; D017136:Ion Transport; D007686:Kidney Tubules, Distal / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D010320:Parvalbumins / Q000032:analysis / Q000276:immunology; D053499:Plasma Membrane Calcium-Transporting ATPases; D011955:Receptors, Drug; D064030:S100 Calcium Binding Protein G / Q000032:analysis / Q000276:immunology; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000032:analysis / Q000276:immunology; D049992:Sodium Chloride Symporters; D019831:Sodium-Calcium Exchanger / Q000032:analysis / Q000276:immunology; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D050916:TRPV Cation Channels
chemical_list: D064026:Calbindins; D015220:Calcium Channels; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D053503:Epithelial Sodium Channels; D010320:Parvalbumins; D011955:Receptors, Drug; D064030:S100 Calcium Binding Protein G; C578875:Slc12a3 protein, mouse; D015222:Sodium Channels; D049992:Sodium Chloride Symporters; D019831:Sodium-Calcium Exchanger; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D050916:TRPV Cation Channels; C492239:TRPV5 protein, human; C492240:Trpv5 protein, mouse; C064415:thiazide receptor; D012964:Sodium; D053499:Plasma Membrane Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium