Regulation of calcium fluxes in pancreatic islets: the role of membrane depolarization.

Abstract

The effect of K+-induced depolarization on calcium fluxes and insulin release from isolated islets were investigated in order to elucidate the mechanism by which glucose initially reduces and later increases 45Ca efflux from prelabeled and perifused rat pancreatic islets. Raising the extracellular K+ concentration from 5.0 to 20.0 mM produced a 2- to 3-fold increase in 45Ca net uptake and efflux from isolated islets. The latter effect was dependent on the presence of extracellular Ca2+, suggesting that it resulted from the entry of calcium into the islet cells. In the presence of 20 mM K+, 16.7 mM glucose failed to stimulate 45Ca efflux, while 20 mM K+ further enhanced 45Ca efflux from islets perifused in the presence of the high concentration of glucose. These findings suggest that the effect of glucose to stimulate 45Ca efflux from perifused islets depends mainly on the glucose-induced depolarization of the cell membrane. In the absence of extracellular calcium, 20 mM K+ failed to mimick the effect of glucose to reduce 45Ca efflux. Glucose (16.7 mM) decreased 45Ca efflux from islets perifused in the presence of 20 mM K+ and antagonized the effect of 20 mM K+ to stimulate 45Ca efflux from perifused islets. It is concluded that K+-induced plasma membrane depolarization reproduces the effect of glucose to stimulate but not to inhibit 45Ca efflux from perifused islets.