Glucose induces closure of single potassium channels in isolated rat pancreatic β-cells

Abstract

The major physiological stimulus for the secretion of insulin from the pancreatic β-cell is an increase in the plasma glucose concentration. It is well established that glucose-stimulated insulin secretion is associated with the appearance of electrical activity in the β-cell^1,2; glucose concentrations above the threshold level for insulin release produce a slow membrane depolarization followed by either oscillatory bursts of action potentials (5–15 mM glucose) or continuous spiking (>16mM glucose). Tracer flux studies³ and microelectrode measurements using intact islets of Langerhans⁴ have indicated that the initial depolarization induced by glucose is caused by a decrease in the resting membrane permeability to potassium. Evidence also suggests that the electrical⁵, ionic⁶ and secretory responses^7,8 to glucose are mediated by the metabolism of the sugar within the β-cell. By using cell-attached membrane patches⁹ from isolated rat pancreatic β-cells, we have now identified a potassium channel (G-channel) that is active at the resting potential and is inhibited by glucose. Closure of this channel requires glucose metabolism. This is the first report of a potassium channel whose activity is modulated by glucose, and which may couple metabolic and ionic events involved in the secretion of insulin.