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The Electrophysiology of the ß-Cell Based on Single Transmembrane Protein Characteristics

Frankfurt Institute for Advanced Studies, Frankfurt, Germany

Correspondence: Address reprint requests to Michael E. Meyer-Hermann, Tel.: 49-69-798-47508; Fax: 49-69-798-47611; E-mail: m.meyer-hermann{at}fias.uni-frankfurt.de.

The electrophysiology of ß-cells is at the origin of insulin secretion. ß-Cells exhibit a complex behavior upon stimulation with glucose including repeated bursts and continuous spiking. Mathematical modeling is most suitable to improve knowledge about the function of various transmembrane currents provided the model is based on reliable data. This is the first attempt to build a mathematical model for the ß-cell electrophysiology in a bottom-up approach that relies on single protein conductance data. The results of previous whole-cell-based models are reconsidered. The full simulation including all prominent transmembrane proteins in ß-cells is used to provide a functional interpretation of their role in ß-cell bursting and an updated vantage point of ß-cell electrophysiology. As a result of a number of in silico knock-out and block experiments the novel model makes some unexpected predictions: single-channel conductance data imply that large-conductance calcium-gated potassium currents acquire the potential of driving oscillations at supralarge glucose levels. A more complex burst interruption model is presented. It also turns out that, depending on the species, sodium currents may be more relevant than considered so far. Experiments are proposed to verify these predictions.