The Relationship between Membrane Potential and Calcium Dynamics in Glucose-Stimulated Beta Cell Syncytium in Acute Mouse Pancreas Tissue Slices

Oscillatory electrical activity is regarded as a hallmark of the pancreatic beta cell glucose-dependent excitability pattern. Electrophysiologically recorded membrane potential oscillations in beta cells are associated with in-phase oscillatory cytosolic calcium activity (Ca²⁺]_i) measured with fluorescent probes. Recent high spatial and temporal resolution confocal imaging revealed that glucose stimulation of beta cells in intact islets within acute tissue slices produces a Ca²⁺]_i change with initial transient phase followed by a plateau phase with highly synchronized Ca²⁺]_i oscillations. Here, we aimed to correlate the plateau Ca²⁺]_i oscillations with the oscillations of membrane potential using patch-clamp and for the first time high resolution voltage-sensitive dye based confocal imaging. Our results demonstrated that the glucose-evoked membrane potential oscillations spread over the islet in a wave-like manner, their durations and wave velocities being comparable to the ones for Ca²⁺]_i oscillations and waves. High temporal resolution simultaneous records of membrane potential and Ca²⁺]_i confirmed tight but nevertheless limited coupling of the two processes, with membrane depolarization preceding the Ca²⁺]_i increase. The potassium channel blocker tetraethylammonium increased the velocity at which oscillations advanced over the islet by several-fold while, at the same time, emphasized differences in kinetics of the membrane potential and the Ca²⁺]_i. The combination of both imaging techniques provides a powerful tool that will help us attain deeper knowledge of the beta cell network.