Document Detail


Gadolinium as an opener of the outwardly rectifying Cl(-) channel (ORCC). Is there relevance for cystic fibrosis therapy?
MedLine Citation:
PMID:  11845315     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There is indirect evidence that the plasmalemma-integrated eukaryotic porin (the voltage-dependent anion-selective channel, VDAC) functions as the outwardly rectifying chloride channel (ORCC). The channel, which is believed to play a role in cell volume regulation, appears to be relevant for cystic fibrosis (CF) therapy, in that it may function as an alternative Cl(-) channel. In the present study we showed first that Gd(3+) altered the voltage dependence of human type-1 porin incorporated into artificial planar lipid bilayers. Next, using a light-scattering approach on transformed normal or CF human B-lymphocytes in hypotonic Ringer solution, we found slightly differing regulatory volume decrease (RVD) curves for the cell lines under study. Addition of 15-60 microM GdCl3 in hypotonic Ringer increased light scattering, pointing to cell swelling beyond normal values. RVD was not observed in those experiments. A corresponding effect was seen in isotonic Ringer containing GdCl3. In either osmotic situation Gd(3+)-induced cell swelling was abolished by monoclonal mouse anti-human type-1 porin antibodies. Agonist and antibody effects were dose dependent. Finally, videocamera-monitored control experiments with adherent HeLa cells verified the direct effect of the agonist on cell swelling in hypo- or isotonic situations and its prevention by the antibodies. We conclude that GdCl3 opens plasmalemma-integrated porin channels, allowing ions to following their gradients, resulting in cell swelling. Since respiratory epithelium expresses porin channels in the apical membrane, the use of gadolinium to activate ORCC may represent a new therapeutic approach in CF.
Authors:
F P Thinnes; G Walter; K P Hellmann; T Hellmann; R Merker; Z Kiafard; J Eben-Brunnen; C Schwarzer; H Götz; N Hilschmann
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Publication Detail:
Type:  Journal Article     Date:  2001-07-07
Journal Detail:
Title:  Pflügers Archiv : European journal of physiology     Volume:  443 Suppl 1     ISSN:  0031-6768     ISO Abbreviation:  Pflugers Arch.     Publication Date:  2001  
Date Detail:
Created Date:  2002-02-14     Completed Date:  2002-05-07     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  0154720     Medline TA:  Pflugers Arch     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  S111-6     Citation Subset:  IM    
Affiliation:
Max-Planck-Institut für Experimentelle Medizin, Abteilung Immunchemie, Hermann-Rein-Strasse 3, 37075 Göttingen, Germany. fthinne@gwdg.de
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MeSH Terms
Descriptor/Qualifier:
Anti-Inflammatory Agents / pharmacology*
Antibodies / pharmacology
Chloride Channels / physiology*
Cystic Fibrosis / drug therapy*,  metabolism*
Gadolinium / pharmacology*
Gluconates / pharmacology
Hela Cells
Humans
Hypotonic Solutions / pharmacology
Ion Channel Gating / drug effects,  physiology
Isotonic Solutions / pharmacology
Porins / immunology,  metabolism
Voltage-Dependent Anion Channels
Water-Electrolyte Balance / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Antibodies; 0/Chloride Channels; 0/Gluconates; 0/Hypotonic Solutions; 0/Isotonic Solutions; 0/Porins; 0/Voltage-Dependent Anion Channels; 10138-52-0/gadolinium chloride; 526-95-4/gluconic acid; 7440-54-2/Gadolinium; 8026-10-6/Ringer's solution

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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