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Decoding myocardial Ca²⁺ signals across multiple spatial scales: a role for sensitivity analysis.

Young-Seon Lee1, Ona Z Liu, Eric A Sobie

  • 1Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY, USA.

Journal of Molecular and Cellular Cardiology
|October 3, 2012
PubMed
Summary

Mathematical models help understand heart calcium (Ca2+) release from the sarcoplasmic reticulum (SR). Parameter sensitivity analysis reveals model capabilities and limitations for future research.

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Area of Science:

  • Cardiovascular Physiology
  • Computational Biology
  • Biophysics

Background:

  • Mathematical modeling is crucial for understanding calcium (Ca2+) release from the sarcoplasmic reticulum (SR) in cardiac cells.
  • Models investigate key phenomena like Ca2+ release triggering and spontaneous SR Ca2+ leak in quiescent heart cells.

Purpose of the Study:

  • To review studies modeling myocardial Ca2+ dynamics across sub-cellular, cellular, and multicellular scales.
  • To evaluate models using parameter sensitivity analysis for understanding their predictive power and limitations.

Main Methods:

  • Summarizing existing literature on mathematical models of cardiac Ca2+ handling.
  • Analyzing models through the lens of parameter sensitivity analysis to assess their behavior and constraints.

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Main Results:

  • Parameter sensitivity analysis provides a framework for understanding model outputs and limitations.
  • This analysis helps define relevant parameters and model outputs, illustrating model capabilities.

Conclusions:

  • Sensitivity analyses are valuable for conceptualizing and comparing different mathematical models of cardiac Ca2+ dynamics.
  • Future studies using sensitivity analyses can simplify complex models and guide experimental design to differentiate between competing hypotheses.