Pancreatic islet cell membrane electrical activity has been studied with intracellular microelectrodes in perifused, isolated mouse islets of Langerhans. The doseresponse effects of glucose and of acetylcholine on the pattern of electrical activity are compared and are shown to be qualitatively different. Electrical activity in the presence of glucose consists of periodic alterations between a polarized silent phase potential and depolarized plateau phase with superimposed rapid spiking activity. Increasing glucose concentration prolongs the plateau phase, at the expense of the silent phase, and thus increases the plateau fraction (the fraction of time in each electrical cycle spent in the plateau phase). By contrast, graded doses of acetylcholine, in the presence of stimulatory levels of glucose, had no effect on plateau fraction. Increasing glucose concentration also slightly reduced the frequency of plateaus, whereas increasing acetylcholine markedly increased plateau frequency. Furthermore, changes of glucose concentration had no effect on the potential levels during the plateau and silent phases, while addition of acetylcholine depolarized the silent phase until, at high concentrations of acetylcholine, the combination of increased plateau frequency and silent phase depolarization produced continuous spiking. Addition of acetylcholine to a slightly substimulatory level of glucose depolarized the membrane without, however, inducing periodic spiking activity. The results suggest that the effects of acetylcholine and glucose are due to different effects on the plateau pacemaker system involved in the regulation Of insulin release.

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