What Is Required for Neuronal Calcium Waves? A Numerical Parameter Study

Markus Breit,Gillian Queisser

doi:10.1186/s13408-018-0064-x

Markus Breit, Gillian Queisser

Open Access

https://doi.org/10.1186/s13408-018-0064-x

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Abstract

Neuronal calcium signals propagating by simple diffusion and reaction with mobile and stationary buffers are limited to cellular microdomains. The distance intracellular calcium signals can travel may be significantly increased by means of calcium-induced calcium release from internal calcium stores, notably the endoplasmic reticulum. The organelle, which can be thought of as a cell-within-a-cell, is able to sequester large amounts of cytosolic calcium ions via SERCA pumps and selectively release them into the cytosol through ryanodine receptor channels leading to the formation of calcium waves. In this study, we set out to investigate the basic properties of such dendritic calcium waves and how they depend on the three parameters dendrite radius, ER radius and ryanodine receptor density in the endoplasmic membrane. We demonstrate that there are stable and abortive regimes for calcium waves, depending on the above morphological and physiological parameters. In stable regimes, calcium waves can travel across long dendritic distances, similar to electrical action potentials. We further observe that abortive regimes exist, which could be relevant for spike-timing dependent plasticity, as travel distances and wave velocities vary with changing intracellular architecture. For some of these regimes, analytic functions could be derived that fit the simulation data. In parameter spaces, that are non-trivially influenced by the three-dimensional calcium concentration profile, we were not able to derive such a functional description, demonstrating the mathematical requirement to model and simulate biochemical signaling in three-dimensional space.

Highlights

Intracellular calcium signals define a transition point between electrical signals and biochemical responses in neurons
Our study focused on: (1) how calcium dynamics depend on the parameters dendrite radius, endoplasmic reticulum (ER) radius, and ryanodine receptor density, (2) whether thresholds can be found for stable calcium waves and (3) on gathering information about wave velocities
In a first series of simulations, we examined how calcium dynamics depend on the ER radius and the density of ryanodine receptor channel (RyR) channels in the ER membrane

Summary

Introduction

Intracellular calcium signals define a transition point between electrical signals and biochemical responses in neurons. Organelle membranes are equipped with calcium exchange mechanisms that allow transport of calcium from the cytosol into the organelles or vice versa Some of these mechanisms—notably the ryanodine receptor channel (RyR) in the ER membrane, which is able to release large amounts of calcium from the ER into the cytosol—have a positive feedback property: Their opening is facilitated by the presence of cytosolic calcium and will trigger the release of even more calcium through surrounding channels. One major question is how the cellular and intracellular architecture can shape and regulate calcium signals that are able to propagate over long distances, for instance in the context of synapse-to-nucleus communication It was shown in [26] that variations in the activation of Ca2+ store release through inositol 1,4,5trisphosphate (IP3) receptors were able to significantly change the calcium wave patterns.

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