Diffusive spatio-temporal noise in a first-passage time model for intracellular calcium release

Area of Science:

• Cellular Biology
• Biophysics
• Computational Biology

Background:

• Intracellular calcium release from the endoplasmic reticulum is regulated by ion channels, generating complex spatio-temporal signals.
• Microscopic fluctuations and stochasticity in ion channel gating contribute to calcium signal dynamics.
• Current models often use deterministic reaction-diffusion equations for calcium distribution, potentially oversimplifying the system.

Purpose of the Study:

• To evaluate the validity of deterministic modeling for intracellular calcium signals.
• To compare a hybrid model (stochastic gating, deterministic calcium) with a fully stochastic model (stochastic gating, stochastic calcium motion).
• To calculate the frequency of localized calcium signals (calcium puffs) from clustered IP3 receptor channels.

Main Methods:

• Developed and compared two computational models: a hybrid stochastic-deterministic model and a fully stochastic model.
• Utilized the two-regime method for efficient simulation of large domains in the fully stochastic model.
• Calculated the first passage time for initial channel opening leading to a calcium puff event.

Main Results:

• Deterministic modeling of calcium concentration significantly overestimates the time between calcium puffs when diffusion is high.
• A fully stochastic model, incorporating Brownian motion of calcium ions, provides more accurate predictions.
• Diffusive noise in intracellular calcium ion concentrations substantially impacts the occurrence of calcium signals.

Conclusions:

• Deterministic models are insufficient for accurately capturing the frequency of calcium puffs, especially with high diffusion rates.
• Stochasticity in calcium ion movement is a critical factor influencing calcium signal dynamics.
• The findings are relevant for understanding cell physiology involving first-passage time problems with low ligand concentrations and high cooperativity.