Sulfonylurea-Binding Sites and ATP-Sensitive K⁺ Channels in α-TC Glucagonoma and β-TC Insulinoma Cells

α-Cells secrete glucagon in a fuel-dependent fashion. We tested the hypothesis that α-cells contain sulfonylurea- and ATP-sensitive K⁺ channels. We studied two clonal lines of α-TC cells (simian virus 40 T-antigen induced glucagonoma cells) and for reference purposes, similarly transformed β-TC insulinoma cells. α-TC cells each contained ∼3000 high-affinity binding sites for the sulfonylurea [³H]glyburide. Whole-cell ATP- and tolbutamide-sensitive K⁺ currents of α-TC and β-TC cells, relative to cell surface area, were comparable. In cell-attached membrane patches of α-TC cells, two types of K⁺ channels were observed. They had slope conductances of ∼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 α-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, α-TC glucagonoma cells contain ATP-sensitive K⁺ channels that regulate glucagon release, yet allow inhibition of hormone release by glucose.