Study of a glucose-activated anion-selective channel in rat pancreatic beta-cells.
Cell-attached channel recordings were made of an inward channel current in isolated rat pancreatic beta-cells incubated in the presence of diazoxide to clamp the membrane potential close to the K(+) equilibrium potential. With 42 mM Cl(-) in the pipette solution, a channel of approximately 200 pS was observed in 20-40% of patches which conducted an inward current at a pipette potential of 0 mV. The channel was activated by a rise in glucose concentration over the range 5-20 mM. The channel was also activated by methylglyoxal, possibly due to its metabolism to D-lactate, but not by the non-metabolizable glucose analogue 3- O-methyl glucose. The channel was activated by hypotonic cell swelling and was sensitive to inhibition by the anion channel blockers 4,4'-dithiocyanatostilbene-2,2'-disulphonic acid, 5-nitro-2-(3-phenylpropylamino) benzoic acid and 4-hydroxytamoxifen. Current reversal occurred at a pipette potential of approximately -67 mV. Raising [Cl(-)] in the pipette solution to 142 mM shifted the reversal potential to -52 mV. It is suggested that the channel is the volume-sensitive anion channel previously described in insulin-secreting cells. Activation of the channel by glucose could be important in generating a depolarizing current leading to increased electrical activity and insulin release, particularly at higher concentrations of glucose where K(ATP) channel activity is minimal.
Best
Leonard
L
Department of Medicine, University of Manchester, Oxford Road, Manchester M13 9WL, UK. lbest@central.cmht.nwest.nhs.uk
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D000838:Anions / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009579:Nitrobenzoates / Q000494:pharmacology; D051381:Rats; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology
D000838:Anions; D004965:Estrogen Antagonists; D007473:Ion Channels; D009579:Nitrobenzoates; D013629:Tamoxifen; C016601:afimoxifene; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D005947:Glucose; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid