Document Detail

Studies of the mechanism of activation of the volume-regulated anion channel in rat pancreatic beta-cells.
MedLine Citation:
PMID:  19669073     Owner:  NLM     Status:  MEDLINE    
There is evidence that depolarization of the pancreatic beta cell by glucose involves cell swelling and activation of the volume-regulated anion channel (VRAC). However, it is unclear whether cell swelling per se or accompanying changes in intracellular osmolality and/or ionic strength are responsible for VRAC activation. VRAC activity was measured in rat beta cells by conventional or perforated patch whole-cell recording. Cell volume was measured by video imaging. In conventional whole-cell recordings, VRAC activation was achieved by exposure of the cells to a hyposmotic bath solution, by application of positive pressure to the pipette, or by use of a hyperosmotic pipette solution. Increased concentrations of intracellular CsCl also caused channel activation, but with delayed kinetics. In perforated patch recordings, VRAC activation was induced by isosmotic addition of the permeable osmolytes urea, 3-O-methyl glucose, arginine, and NH4Cl. These effects were all accompanied by beta-cell swelling. It is concluded that increased cell volume, whether accompanied by raised intracellular osmolality or ionic strength, is a major determinant of VRAC activation in the beta cell. However, increased intracellular ionic strength markedly reduced the rate of VRAC activation. These findings are consistent with the hypothesis that the accumulation of glucose metabolites in the beta cell, and the resultant increase in cell volume, provides a signal coupling glucose metabolism with VRAC activation.
Len Best; Peter D Brown
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Publication Detail:
Type:  Journal Article     Date:  2009-08-08
Journal Detail:
Title:  The Journal of membrane biology     Volume:  230     ISSN:  1432-1424     ISO Abbreviation:  J. Membr. Biol.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-08-27     Completed Date:  2009-11-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0211301     Medline TA:  J Membr Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  83-91     Citation Subset:  IM    
School of Medicine, Manchester Royal Infirmary, University of Manchester, Oxford Road, Manchester M139WL, UK.
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MeSH Terms
Cells, Cultured
Chloride Channels / physiology*
Insulin-Secreting Cells
Ion Channel Gating / physiology*
Membrane Potentials / physiology*
Rats, Sprague-Dawley
Reg. No./Substance:
0/Chloride Channels

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