Paradoxical activation by glucose of quinine-sensitive potassium channels in the pancreatic B-cell

Abstract

A stepwise rise in extracellular glucose concentration from 8.3 to 16.7 mM paradoxically increases the outflow of 86Rb from prelabelled pancreatic islets, as if the permeability to K + of the plasma membrane was suddenly and sustainedly increased. The mechanisms underlying this paradoxical response was investigated by exposing the islets to agents blocking either the Ca 2+-activated or voltage-sensitive K + channels. At concentrations exerting similar inhibitory effects upon the K + permeability of glucose-deprived islets, tetraethylammonium failed to affect, while quinine severely impaired the increase in 86Rb efflux induced by the rise in glucose concentration. None of these drugs impeded the stimulation of Ca 2+ influx evoked by the rise in glucose concentration. These findings suggest that glucose, in the 8.3–16.7 mM range, facilitates K + efflux from the pancreatic B-cell by stimulating a Ca 2+-sensitive modality of K + extrusion.