[Regulation of potassium channels in insulin secreting cells]

Glucose is the single most important signal for stimulating insulin secretion from the B-cells in the pancreatic islets. An increase in the plasma glucose concentration causes a reduction of the electrical potential difference across the plasma membrane (membrane depolarization), and this is mediated by closure of adenosine triphosphate (ATP)-sensitive K+ channels. This depolarization opens voltage-gated Ca2+ channels through which Ca2+ enters, elevating the free intracellular Ca2+ concentration, and this signal stimulates insulin secretion by exocytosis (granule fusion with plasma membrane and opening at point of fusion). The increased intracellular Ca2+ concentration evokes opening of Ca2+- and voltage-activated K+ channels with a high unit conductance, and this results in membrane repolarization. The repolarization closes the Ca2+ channels and Ca2+ inflow ceases. The stimulus for opening the Ca2+-activated K+ channels therefore disappears and they close, resulting in renewed depolarization and reopening of the Ca2+ channels. This cycle of channel openings and closures results in repetitive firing of Ca2+ action potentials, causing waves of Ca2+ inflow that stimulate insulin secretion. Reducing the extracellular glucose concentration below the normal resting level evokes reopening of the ATP-sensitive K+ channels and closure of the other channels, reestablishing the resting situation.