Evidence for modulation of cell-to-cell electrical coupling by cAMP in mouse islets of Langerhans

The effects of forskolin on electrical coupling among pancreatic beta-cells were studied. Two microelectrodes were used to measure membrane potentials simultaneously in pairs of islet beta-cells. Intracellular injection of a current pulse (delta I) elicited a membrane response delta V1 in the injected cell and also a response delta V2 in a nearby beta-cell confirming the existence of cell-to-cell electrical coupling among islet beta-cells. In the presence of glucose (7 mM), application of forskolin evoked a transient depolarization of the membrane and electrical activity suggesting that the drug induced a partial inhibition of the beta-cell membrane K+ conductance. Concomitant with this depolarization of the membrane there was a marked decrease in beta-cell input resistance (delta V2/delta I) suggesting that exposure to forskolin enhanced intercellular coupling. Direct measurements of the coupling ratio delta V2/delta V1 provided further support to the idea that forskolin enhances electrical coupling among islet cells. Indeed, application of forskolin reversibly increased the coupling ratio. These results suggest that cAMP might be involved in the modulation of electrical coupling among islet beta-cells.