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Cooperativity can reduce stochasticity in intracellular calcium dynamics
Kai Wang1, Wouter-Jan Rappel, Herbert Levine
1Department of Physics and Center for Theoretical Biological Physics, University of California, San Diego, La Jolla, CA 92093-0319, USA.
Physical Biology
|October 6, 2005
Summary
A mathematical model reveals that slowly activating pumps in the endoplasmic reticulum increase calcium wave cooperativity. This explains experimental data showing reduced standard deviations in calcium wave intervals, unlike models with instantaneous pump activation.
Area of Science:
- Cellular Biology
- Biophysics
- Mathematical Modeling
Background:
- Intracellular calcium waves, triggered by inositol (1,4,5)-triphosphate (IP3) receptor openings on the endoplasmic reticulum, exhibit precise timing.
- Experimental data from Xenopus oocytes show unusually low standard deviations in calcium wave intervals and a slow rise in background calcium.
- Existing models assuming instantaneous pump activation fail to replicate these observed inter-wave interval distributions and background calcium dynamics.
Purpose of the Study:
- To investigate the role of slow pump activation in the endoplasmic reticulum on calcium wave cooperativity.
- To determine if a mathematical model incorporating slow pump activation can explain experimental observations of calcium wave intervals and background calcium.
- To elucidate the mechanisms underlying the precise timing and cooperativity of intracellular calcium signaling.
Main Methods:
- Development and analysis of a simple mathematical model simulating calcium release through IP3 receptors on the endoplasmic reticulum.
- Comparison of model predictions with experimental data on inter-wave intervals and background calcium concentration dynamics in Xenopus oocytes.
- Inclusion of two distinct pump activation mechanisms: instantaneous and slow activation.
Main Results:
- A model with instantaneous pump activation predicted independent cluster firing and a Poisson distribution for inter-wave intervals (standard deviation ≈ mean).
- Incorporating slowly activating pumps resulted in a gradual increase in background calcium concentration.
- This slow activation mechanism enhanced cooperativity, making global calcium events more probable and leading to reduced standard deviations and non-Poisson inter-wave interval distributions.
Conclusions:
- Slow activation of endoplasmic reticulum pumps is crucial for generating the observed cooperativity in calcium wave events.
- The model incorporating slow pump activation successfully explains the experimentally observed precise inter-wave intervals and non-Poisson distributions.
- This finding highlights the importance of pump dynamics in regulating intracellular calcium signaling and wave propagation.
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