Potassium channels of the insulin‐secreting B cell

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Abstract
Summary—Ionic and electrical events play a central role in the stimulus‐secretion coupling of the pancreatic B cell. Potassium permeability is critically involved in the regulation of B cell membrane potential and insulin secretion. In the absence of glucose, membrane potential remains stable, around − 65 mV. This resting potential is mainly determined by the high potassium conductance of the membrane. The ATP generated by glucose metabolism in B cells blocks the K+(ATP)channels controlling resting membrane potential. Thus, glucose metabolism leads to closure of the ATP‐dependent potassium channels; the resulting decrease in K+ permeability induces depolarization and opening of voltage‐activated Ca‐channels. The subsequent increase in Ca2+influx raises the cytoplasmic concentration of free Ca2+. which in turn triggers exocytosis of secretory granules. Other types of K+ channels have also been identified in the B cell, such as voltage‐ and Ca2+‐dependent K+ channels, which are not a target for the action of glucose, but may play a role in the repolarization of spikes. The modulation of insulin release by some hormones and neurotransmitters involves, among other mechanisms, an interference with the plasma membrane K+ conductance. Thus, galanine, somatostatin and adrenaline, which inhibit insulin release, increase K+ conductance by a G protein‐dependent mechanism; both peptides were reported to open ATP‐sensitive K+ channels in insulin‐secreting cell line RINm5F. It was also observed that extracellular purine nucleotides could interfere with K+ channels. Among the various drugs interfering with insulin secretion, sulfonylureas, such as tolbutamide and glibenclamide, directly inhibit ATP‐dependent K+ channels in the B cell membrane and thereby initiate insulin release. In contrast, potassium channel openers such as diazoxide, antagonize the effects of glucose by increasing K+ permeability of the B cell membrane. Furthermore, other classes of drugs have recently been shown to interact with K+(ATP)channels. Thus, K+ channels of the pancreatic B cell, particularly ATP‐dependent ones, play a crucial role in the electrophysiology of insulin secretion; they are an important target for pharmacological agents designed to modulate this secretion.

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