Emergence of regular and complex calcium oscillations by inositol 1,4,5-trisphosphate signaling in astrocytes

TL;DR

This paper uses bifurcation theory to analyze how inositol 1,4,5-trisphosphate (IP3) signaling leads to various calcium oscillations in astrocytes, from single-cell to coupled and spatially extended models.

Contribution

It provides a mathematical framework for understanding the emergence of regular and complex calcium oscillations through bifurcation analysis in astrocyte models.

Findings

Identification of IP3 pathways causing bifurcations in calcium dynamics

Demonstration of chaotic oscillations in coupled astrocyte models

Insights into mechanisms of spatially-confined calcium oscillations

Abstract

We use tools of bifurcation theory to characterize dynamics of astrocytic~IP$_3$ and~Ca$^{2+}$ for different~IP$_3$ regimes from a mathematical point of view. We do so following a bottom-up approach, starting from a compact, well-stirred astrocyte model to first identify characteristic~IP$_3$ pathways whereby~Ca$^{2+}$ (and~IP$_3$) dynamics "bifurcate", namely change from stable (constant) concentration levels, to oscillatory dynamics. Then we extend our analysis to the elemental case of two astrocytes, coupled by~IP$_3$ diffusion mediated by gap junction channels, putting emphasis on the mechanisms of emergence of chaotic oscillations. Finally, we complete our analysis discussing spatiotemporal~Ca$^{2+}$ dynamics in a spatially-extended astrocyte model, gaining insights on the possible physical mechanisms whereby random Ca$^{2+}$~generation could be orchestrated into robust, spatially-confined intracellular~Ca$^{2+}$ oscillations.