Although isolated rat islets are widely used to study in vitro insulin secretion and the underlying metabolic and ionic processes, knowledge on the properties of glucose-induced electrical activity (GIEA), a key step in glucose-response coupling, has been gathered almost exclusively from microdissected mouse islets. Using a modified intracellular recording technique, we have now compared the patterns of GIEA in collagenase-isolated rat and mouse islets. Resting membrane potentials of rat and mouse beta -cells mere approximately -50 and -60 mV, respectively Both rat and mouse beta -cells displayed prompt membrane depolarizations in response to glucose. However, whereas the latter exhibited a bursting pattern consisting of alternating hyperpolarized and depolarized active phases, rat beta -cells fired action potentials from a nonoscillating membrane potential at all glucose concentrations (8.4-22.0 mmol/l). This was mirrored by changes in the intracellular Ca concentration ([Ca2+](i)), which was oscillatory in mouse and nonoscillatory in rat islets. Stimulated rat beta -cells were strongly hyperpolarized by diazoxide, an activator of ATP-dependent K+ channels. Glucose evoked dose-dependent depolarizations and [Ca2+](i) increases in both rat (EC50 5.9-6.9 mmol/l) and mouse islets (EC50 8.3-9.5 mmol/l), although it did not affect the burst plateau potential in the latter case. We conclude that there are important differences between beta -cells from both species with respect to early steps in the stimulus-secretion coupling cascade based on the following findings: 1) mouse beta -cells have a larger resting K+ conductance in 2 mmol/l glucose, 2) rat beta -cells lack the compensatory mechanism responsible for generating membrane potential oscillations and holding the depolarized plateau potential. in mouse beta -cells, and 3) the electrical and [Ca2+](i) dose-response curves in rat beta -cells are shifted toward lower glucose concentrations. Exploring the molecular basis of these differences may clarify several a priori assumptions on the electrophysiological properties of rat beta -cells, which could foster the development of new working models of pancreatic beta -cell function.
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