Sulfonylurea-binding sites and ATP-sensitive K+ channels in alpha-TC glucagonoma and beta-TC insulinoma cells.
alpha-Cells secrete glucagon in a fuel-dependent fashion. We tested the hypothesis that alpha-cells contain sulfonylurea- and ATP-sensitive K+ channels. We studied two clonal lines of alpha-TC cells (simian virus 40 T-antigen induced glucagonoma cells) and for reference purposes, similarly transformed beta-TC insulinoma cells. alpha-TC cells each contained approximately 3000 high-affinity binding sites for the sulfonylurea [3H]glyburide. Whole-cell ATP- and tolbutamide-sensitive K+ currents of alpha-TC and beta-TC cells, relative to cell surface area, were comparable. In cell-attached membrane patches of alpha-TC cells, two types of K+ channels were observed. They had slope conductances of approximately 63 and 33 pS when the electrode contained 151 mM K+. Tolbutamide and diazoxide decreased and enhanced, respectively, the open probability of these channels. The membrane of alpha-TC cells depolarized periodically. This electrical activity was inhibited by diazoxide. A physiological mixture of amino acids enhanced glucagon release, and high glucose partially inhibited this release. Tolbutamide also enhanced glucagon release, whereas diazoxide inhibited it. Thus, alpha-TC glucagonoma cells contain ATP-sensitive K+ channels that regulate glucagon release, yet allow inhibition of hormone release by glucose.
Ronner
P
P
Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia 19104-6015.
Matschinsky
F M
FM
Hang
T L
TL
Epstein
A J
AJ
Buettger
C
C
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D003981:Diazoxide / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism; D005935:Glucagonoma; D005905:Glyburide / Q000378:metabolism*; D007340:Insulinoma; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D010190:Pancreatic Neoplasms; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014044:Tolbutamide / Q000494:pharmacology*; D014316:Tritium; D014407:Tumor Cells, Cultured
D015221:Potassium Channels; D014316:Tritium; D000255:Adenosine Triphosphate; D005934:Glucagon; D014044:Tolbutamide; D003981:Diazoxide; D005905:Glyburide