Stochastic effects in intercellular calcium spiking in hepatocytes

Area of Science:

• Cellular biology
• Biophysics
• Computational biology

Background:

• Intercellular calcium (Ca2+) waves are crucial for cell communication.
• Previous models often simplified stochastic effects in wave propagation.
• Gap junctions play a key role in mediating these signals via second messengers.

Purpose of the Study:

• To investigate the impact of stochastic effects on two models of intercellular calcium wave propagation.
• To compare simulation results with experimental observations in rat hepatocytes.
• To analyze the influence of gap junction diffusion on wave synchronization.

Main Methods:

• Monte Carlo simulation of stochastic processes.
• Modeling intercellular calcium wave propagation using two distinct models.
• Analysis of gap junction diffusion and second messenger dynamics.

Main Results:

• Stochastic effects generally enhance model-experiment agreement for optimized parameters.
• Both models exhibit baseline Ca2+ fluctuations and peak height variations.
• One model shows a distribution of latency times, matching experimental spike width observations.
• Another model demonstrates independent initial oscillations that synchronize over time, especially with low gap junction diffusion.

Conclusions:

• Stochastic modeling provides a more accurate representation of intercellular calcium wave dynamics.
• The interplay between gap junction diffusion and stochasticity influences wave synchronization and timing.
• These findings offer insights into cellular signaling mechanisms and potential therapeutic targets.