The topography of electrical synchrony among beta-cells in the mouse islet of Langerhans.

Abstract

beta-Cells in microdissected islets of Langerhans produce rhythmical bursts of electrical activity. This was monitored with two micro-electrodes simultaneously and the frequency and phase (collectively referred to as synchrony) of the two signals was investigated. At any instant two impaled cells produced bursts of the same frequency even when separated by up to 400 micron. When the electrode tips were separated by less than about 20 micron and current injection showed the cells to be ionically coupled the two signals were in phase and had almost identical shape. The phase relations between cells further apart were variable, the leading cell usually being located deeper within the islet than the other impaled cell. Increasing the glucose concentration increased electrical activity, reduced any phase lags and made the shape of the bursts more similar. There was less lag between the responses from two cells when the glucose concentration was suddenly reduced, than when it was suddenly increased. Qualitatively similar observations were made in glibenclamide-treated mice, a treatment previously shown to increase dye coupling between islet cells. However, the response to increasing glucose concentrations showed less phase lag; likewise the phase lag between bursts was reduced. Furthermore the response to current injected into one cell could be detected at much larger distances (up to 80 micron) than in control islets. This suggests that electrical coupling of beta-cells was improved in sulphonylurea-treated mice. Electron microscopy of both control and glibenclamide-treated mouse islets fixed at the end of each electrophysiological experiment showed the region impaled by the electrodes to be well preserved and, whenever the electrodes penetrated at least 20 micron into the islet, to contain a large proportion of beta-cells. The data support the view that, within an islet, most but not necessarily all cells are electrically synchronized, and that the coupling can be modulated by natural and pharmacological secretagogues.