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

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 Ca²⁺-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 Ca²⁺ 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 Ca²⁺-sensitive modality of K⁺ extrusion.