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Simulation of developmental changes in action potentials with ventricular cell models.
Hitomi Itoh1, Yasuhiro Naito, Masaru Tomita
1Institute for Advanced Biosciences, Keio University, Fujisawa, Kanagawa, 252-8520, Japan, ducky@sfc.keio.ac.jp.
Systems and Synthetic Biology
|November 13, 2008
Summary
Mathematical models revealed how cardiomyocyte action potentials change during development. Simulating ionic currents showed spontaneous activity in early cells, which was lost in later stages, matching experimental observations.
Area of Science:
- Cardiology
- Developmental Biology
- Computational Biology
Background:
- Early embryonic ventricular cells exhibit spontaneous activity.
- This activity diminishes in later developmental stages.
- Action potential changes are driven by alterations in ionic currents.
Purpose of the Study:
- To develop a mathematical model simulating rodent ventricular cell action potentials across developmental stages.
- To understand the role of ionic currents, pumps, exchangers, and sarcoplasmic reticulum Ca(2+) kinetics in cardiomyocyte development.
Main Methods:
- Quantitative changes in ionic systems were represented as relative activities.
- These activities were multiplied by conductance or conversion factors.
- Mathematical equations were used to simulate action potentials at early embryonic, late embryonic, and neonatal stages.
Main Results:
- The model successfully simulated spontaneous activity in early embryonic ventricular cells.
- Spontaneous activity was absent in simulated late embryonic and neonatal ventricular cells.
- Simulated action potentials aligned with in vitro experimental data.
Conclusions:
- A common set of mathematical equations can reproduce rodent ventricular cell action potentials across development.
- Relative activities of ionic currents, pumps, exchangers, and SR Ca(2+) kinetics are key to developmental changes.
- This modeling approach enhances understanding of cardiomyocyte development and electrophysiology.
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