Ca2+ Microdomains in the Pancreatic Beta-Cell: a Three-Dimensional Modeling Approach

Abstract

Beta-cells are responsible for secreting insulin as a response to an increase in blood glucose levels. Being electrically excitable, beta-cells exhibit electrical activity in response to a glucose stimulus driven by a well established mechanism involving glucose metabolism, ionic channels and calcium signaling. The purpose of beta-cell electrical activity is to allow the influx of Ca2+ through ionic channels located in the plasma membrane in order to generate a high Ca2+В  icrodomain, which is the key signal triggering insulin exocytosis. It is known that Ca2+ channels and insulin granules co-localize, and that they are not evenly distributed over the cell. Accounting for these morphological haracteristics we have developed a three-dimensional model of a beta-cell. By including a mathematical description of the ionic channels, our model reproduces the electrical activity observed experimentally. This allow us to simulate the spatiotemporal distribution of Ca2+ in the microdomain generated by the electrical activity pattern. Our modeling approach enable us to evaluate the effect of distinct distributions of Ca2+ channels over the cell membrane. Besides reproducing experimental observations, we also assess the impact of impaired functioning of ionic channels on Ca2+ microdomains, which could ultimately affect insulin secretion.