Ion Channel Signal Transduction in Pancreatic β-Cells

Publisher Summary Plasma membrane ion channels are protein tunnels on the surface of cells that permit cellular entry and exit of electrically charged ions. Depending on the signal that makes them open and close (“gating”), ion channels can be classified into ligand-gated and voltage-gated channels. Although these molecules are better known for their role in generating the spark of the heartbeat or in the lightning-like conduction of nerve action potentials, it is now evident that ion channels play a critical role in igniting the physiological process of insulin secretion in pancreatic β-cells. Recognition of a signal at the cell surface and its translation into an intracellular gesture defines the process of “signal transduction.” This chapter describes how signal transduction by specific ion channels mediates the stimulus-secretion coupling process in insulin-secreting β-cells. The primary physiological function of the pancreatic β-cell is to sense changes in circulating glucose levels and respond with an appropriate insulin secretory response. The significance of this apparently simple function is of profound importance in health because its failure disrupts normal blood glucose homeostasis and results in important insulin secretory abnormalities such as diabetes mellitus and familial hyperinsulinism. The β-cell is rather unique because its electrical activity changes in response to stimuli that are primarily metabolic in nature. Thus, examination of the electrical events in β-cell stimulus-secretion coupling is best understood by following the changes in response to its primary metabolic stimulus, glucose.