Membrane Potential-Dependent Inactivation of Voltage-Gated Ion Channels in -Cells Inhibits Glucagon Secretion From Human Islets

OBJECTIVE—To document the properties of the voltage-gated ion channels in human pancreatic -cells and their role in glucagon release. RESEARCH DESIGN AND METHODS—Glucagon release was measured from intact islets. [Ca2]i was recorded in cells showing spontaneous activity at 1 mmol/l glucose. Membrane currents and potential were measured by whole-cell patch-clamping in isolated -cells identified by immunocytochemistry. RESULTS—Glucose inhibited glucagon secretion from human islets; maximal inhibition was observed at 6 mmol/l glucose. Glucagon secretion at 1 mmol/l glucose was inhibited by insulin but not by ZnCl2. Glucose remained inhibitory in the presence of ZnCl2 and after blockade of type-2 somatostatin receptors. Human -cells are electrically active at 1 mmol/l glucose. Inhibi-tion of KATP-channels with tolbutamide depolarized -cells by 1