title: Acid incubation reverses the polarity of intercalated cell transporters, an effect mediated by hensin.
abstract: Metabolic acidosis causes a reversal of polarity of HCO(3)(-) flux in the cortical collecting duct (CCD). In CCDs incubated in vitro in acid media, beta-intercalated (HCO(3)(-)-secreting) cells are remodeled to functionally resemble alpha-intercalated (H(+)-secreting) cells. A similar remodeling of beta-intercalated cells, in which the polarity of H(+) pumps and Cl(-)/HCO(3)(-) exchangers is reversed, occurs in cell culture and requires the deposition of polymerized hensin in the ECM. CCDs maintained 3 h at low pH ex vivo display a reversal of HCO(3)(-) flux that is quantitatively similar to an effect previously observed in acid-treated rabbits in vivo. We followed intracellular pH in the same beta-intercalated cells before and after acid incubation and found that apical Cl/HCO(3) exchange was abolished following acid incubation. Some cells also developed basolateral Cl(-)/HCO(3)(-) exchange, indicating a reversal of intercalated cell polarity. This adaptation required intact microtubules and microfilaments, as well as new protein synthesis, and was associated with decreased size of the apical surface of beta-intercalated cells. Addition of anti-hensin antibodies prevented the acid-induced changes in apical and basolateral Cl(-)/HCO(3)(-) exchange observed in the same cells and the corresponding suppression of HCO(3)(-) secretion. Acid loading also promoted hensin deposition in the ECM underneath adapting beta-intercalated cells. Hence, the adaptive conversion of beta-intercalated cells to alpha-intercalated cells during acid incubation depends upon ECM-associated hensin.
authors.affiliation: Department of Pediatrics and Strong Children's Research Center, University of Rochester School of Medicine, Rochester, New York 14642, USA. George_Schwartz@urmc.rochester.edu
authors.forename: George J
authors.initials: GJ
authors.lastname: Schwartz
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tsuruoka
authors.forename: Soundarapandian
authors.initials: S
authors.lastname: Vijayakumar
authors.forename: Snezana
authors.initials: S
authors.lastname: Petrovic
authors.forename: Ayesa
authors.initials: A
authors.lastname: Mian
authors.forename: Qais
authors.initials: Q
authors.lastname: Al-Awqati
mesh_terms: D000136:Acid-Base Equilibrium; D000138:Acidosis / Q000378:metabolism; D000818:Animals; D016764:Cell Polarity; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D017136:Ion Transport; D007672:Kidney Cortex / Q000166:cytology / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins; D017494:Proton Pumps / Q000378:metabolism; D011817:Rabbits; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
chemical_list: D027963:Chloride-Bicarbonate Antiporters; D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins; D017494:Proton Pumps; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C495130:hensin protein, rabbit