A phenomenological cluster-based model of Ca2+ waves and oscillations for Inositol 1,4,5-trisphosphate receptor (IP3R) channels

TL;DR

This paper presents a minimal reaction-diffusion model of IP3 receptor clusters that captures calcium release patterns like puffs, waves, and oscillations, providing insights into their underlying mechanisms and dynamics.

Contribution

It introduces a reduced reaction-diffusion model of IP3 receptors that explains calcium signaling patterns through bifurcation analysis and phase diagrams.

Findings

The model exhibits excitable, bistable, and oscillatory dynamics.

Bifurcation analysis explains pattern emergence and transitions.

Wave speed and oscillation period are quantified in relation to system parameters.

Abstract

Clusters of IP3 receptor channels in the membranes of the endoplasmic reticulum (ER) of many non-excitable cells release calcium ions in a cooperative manner giving rise to dynamical patterns such as Ca2+ puffs, waves, and oscillations that occur on multiple spatial and temporal scales. We introduce a minimal yet descriptive reaction-diffusion model of IP3 receptors for a saturating concentration of IP3 using a principled reduction of a detailed Markov chain description of individual channels. A dynamical systems analysis reveals the possibility of excitable, bistable and oscillatory dynamics of this model that correspond to three types of observed patterns of calcium release -- puffs, waves, and oscillations respectively. We explain the emergence of these patterns via a bifurcation analysis of a coupled two-cluster model, compute the phase diagram and quantify the speed of the waves and period of oscillations in terms of system parameters. We connect the termination of large-scale Ca2+ release events to IP3 unbinding or stochasticity.