The electrophysiology of the -cell based on single transmembrane protein characteristics

¹ Frankfurt Institute for Advanced Studies (FIAS)

^* To whom correspondence should be addressed. E-mail: m.meyer-hermann{at}fias.uni-frankfurt.de.

Submitted on February 8, 2007
Revised on March 7, 2007
Accepted on 31 May 2007

	Abstract

The electrophysiology of -cells is at the origin of insulin secretion. -cells exhibit a complex behaviour upon stimulation with glucose including repeated bursts and continuous spiking. Mathematical modelling 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 -cell-electrophysiology in a bottom-up approach which relies on single protein conductivity data. The results of previous whole-cell-based models are reconsidered. The full simulation including all prominent transmembrane proteins in -cells is used to provide a functional interpretation of their role in -cell-bursting and an updated vantage point of -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 conductivity data imply that large-conductance calcium-gated potassium currents acquire the potential of driving oscillations at supra-large 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.

Key Words: ATPases, calcium dynamics, electrical bursting, insulin secretion, ion-channels, mathematical modelling