Oscillatory Membrane Potential Response to Glucose in Islet β-Cells: A Comparison of Islet-Cell Electrical Activity in Mouse and Rat

Abstract

In contrast to mouse, rat islet β-cell membrane potential is reported not to oscillate in response to elevated glucose despite demonstrated oscillations in calcium and insulin secretion. We aim to clarify the electrical activity of rat islet β-cells and characterize and compare the electrical activity of both α- and β-cells in rat and mouse islets. We recorded electrical activity from α- and β-cells within intact islets from both mouse and rat using the perforated whole-cell patch clamp technique. Fifty-six percent of both mouse and rat β-cells exhibited an oscillatory response to 11.1 mm glucose. Responses to both 11.1 mm and 2.8 mm glucose were identical in the two species. Rat β-cells exhibited incremental depolarization in a glucose concentration-dependent manner. We also demonstrated electrical activity in human islets recorded under the same conditions. In both mouse and rat α-cells 11 mm glucose caused hyperpolarization of the membrane potential, whereas 2.8 mm glucose produced action potential firing. No species differences were observed in the response of α-cells to glucose. This paper is the first to demonstrate and characterize oscillatory membrane potential fluctuations in the presence of elevated glucose in rat islet β-cells in comparison with mouse. The findings promote the use of rat islets in future electrophysiological studies, enabling consistency between electrophysiological and insulin secretion studies. An inverse response of α-cell membrane potential to glucose furthers our understanding of the mechanisms underlying glucose sensitive glucagon secretion.