GLUTAMATE-INDUCED CALCIUM SIGNALING IN ASTROCYTE NETWORKS

We present an astrocyte network model capturing the internal calcium and inositol triphosphate (IP3) dynamics of astrocytes coupled via gap junctions (Ullah et al. 2006). The emergence of global calcium events is found to be initiated by local excess glutamate, which may be related to the decreased efficacy of the glutamate transporter (GLT-1). We show that glutamate delivers a switching mechanism that triggers the propagation of calcium waves in the astrocyte network. The onset of the calcium events is identified as a supercritical Hopf bifurcation with subsequent explosive amplitude growth due to an internal feedback mechanism involving the release of calcium from the endoplasmic reticulum (ER). The ER buffer releases calcium through an IP3-regulated process called calcium-induced calcium release. The released calcium can trigger calcium waves in the astrocyte network through coupling via gap junctions. Once cytosolic calcium levels are elevated, the feedback cycle terminates through the deactivation of IP3 receptors by calcium. The upregulation of GLT-1 may prevent local calcium events from occurring due to a reduction of extracellular glutamate and decreased IP3 production. However, it may be insufficient to prevent the propagation of calcium events once events are triggered locally due to astrocytic communication through gap junctions. We investigate this idea in our model by adding homogeneous extracellular glutamate, which mimics decreased GLT-1 efficacy and captures the impact on the transformation from local to global calcium events. Through mathematical modeling, we shed light on the intricate relation between glutamate and astrocytic calcium dynamics.

Schematic: Gap-junctions facilitate calcium waves.