Simulation of developmental changes in action potentials with ventricular cell models |
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Authors: | Hitomi Itoh Yasuhiro Naito Masaru Tomita |
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Institution: | (1) Institute for Advanced Biosciences, Keio University, Fujisawa Kanagawa, 252-8520, Japan;(2) Bioinformatics Program, Graduate School of Media and Governance, Keio University, Fujisawa Kanagawa, 252-8520, Japan;(3) Japan Society for the Promotion of Science (DC1), Tokyo, Japan;(4) Department of Environmental Information, Keio University, Fujisawa Kanagawa, 252-8520, Japan |
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Abstract: | During cardiomyocyte development, early embryonic ventricular cells show spontaneous activity that disappears at a later stage.
Dramatic changes in action potential are mediated by developmental changes in individual ionic currents. Hence, reconstruction
of the individual ionic currents into an integrated mathematical model would lead to a better understanding of cardiomyocyte
development. To simulate the action potential of the rodent ventricular cell at three representative developmental stages,
quantitative changes in the ionic currents, pumps, exchangers, and sarcoplasmic reticulum (SR) Ca2+ kinetics were represented as relative activities, which were multiplied by conductance or conversion factors for individual
ionic systems. The simulated action potential of the early embryonic ventricular cell model exhibited spontaneous activity,
which ceased in the simulated action potential of the late embryonic and neonatal ventricular cell models. The simulations
with our models were able to reproduce action potentials that were consistent with the reported characteristics of the cells
in vitro. The action potential of rodent ventricular cells at different developmental stages can be reproduced with common
sets of mathematical equations by multiplying conductance or conversion factors for ionic currents, pumps, exchangers, and
SR Ca2+ kinetics by relative activities. |
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Keywords: | Cardiac ventricular cell Computer modeling Development Electrophysiology Ion channels Spontaneous electrical activity |
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