Document Detail

Acid incubation reverses the polarity of intercalated cell transporters, an effect mediated by hensin.
MedLine Citation:
PMID:  11781354     Owner:  NLM     Status:  MEDLINE    
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.
George J Schwartz; Shuichi Tsuruoka; Soundarapandian Vijayakumar; Snezana Petrovic; Ayesa Mian; Qais Al-Awqati
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  109     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2002-01-08     Completed Date:  2002-02-11     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  89-99     Citation Subset:  AIM; IM    
Department of Pediatrics and Strong Children's Research Center, University of Rochester School of Medicine, Rochester, New York 14642, USA.
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MeSH Terms
Acid-Base Equilibrium
Acidosis / metabolism
Cell Polarity
Chloride-Bicarbonate Antiporters / metabolism*
Extracellular Matrix / metabolism
Extracellular Matrix Proteins
Hydrogen-Ion Concentration
Ion Transport
Kidney Cortex / cytology,  metabolism
Kidney Tubules, Collecting / cytology,  metabolism*
Membrane Proteins*
Proton Pumps / metabolism
Receptors, Immunologic / metabolism*
Receptors, Lipoprotein*
Receptors, Scavenger
Scavenger Receptors, Class B
Grant Support
Reg. No./Substance:
0/Chloride-Bicarbonate Antiporters; 0/Extracellular Matrix Proteins; 0/Membrane Proteins; 0/Proton Pumps; 0/Receptors, Immunologic; 0/Receptors, Lipoprotein; 0/Receptors, Scavenger; 0/Scarb1 protein, mouse; 0/Scavenger Receptors, Class B; 0/hensin protein, rabbit

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