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Simulation of developmental changes in action potentials with ventricular cell models.

Itoh H, Naito Y, Tomita M - Syst Synth Biol (2007)

Bottom Line: 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 Ca(2+) kinetics by relative activities.

View Article: PubMed Central - PubMed

Affiliation: Institute for Advanced Biosciences, Keio University, Fujisawa, Kanagawa, 252-8520, Japan, ducky@sfc.keio.ac.jp.

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) Ca(2+) 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 Ca(2+) kinetics by relative activities.

No MeSH data available.


Related in: MedlinePlus

Effects of shifting relative activities of all current components (A), IK1 (B), IKr (C), and of all current components except IK1 and IKr (D). (A) Changes in action potential when shifting relative activities of all currents by 10% increments. (B) Changes in action potential when shifting from relative activity of early embryonic IK1 (darkest line) to that of late embryonic IK1 (lightest line) by 10% increments. Spontaneous action potential ceased when relative activity of IK1 was shifted by 10% (red line) or more toward late embryonic stage value. Dataset could not be obtained when the current was shifted by 90% and 100% toward the late embryonic stage value, owing to collapse in the balance of the ionic concentration. (C) Changes in action potential when shifting from relative activity of early embryonic IKr (darkest line) to that of late embryonic IKr (lightest line) by 10% increments. Spontaneous action potential ceased when relative activity of IKr was shifted by 80% (red line) or more toward late embryonic stage value. (D). Changes in action potential when relative activities of all currents except IK1 and IKr were shifted from early embryonic to late embryonic values by 10% increments
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Fig4: Effects of shifting relative activities of all current components (A), IK1 (B), IKr (C), and of all current components except IK1 and IKr (D). (A) Changes in action potential when shifting relative activities of all currents by 10% increments. (B) Changes in action potential when shifting from relative activity of early embryonic IK1 (darkest line) to that of late embryonic IK1 (lightest line) by 10% increments. Spontaneous action potential ceased when relative activity of IK1 was shifted by 10% (red line) or more toward late embryonic stage value. Dataset could not be obtained when the current was shifted by 90% and 100% toward the late embryonic stage value, owing to collapse in the balance of the ionic concentration. (C) Changes in action potential when shifting from relative activity of early embryonic IKr (darkest line) to that of late embryonic IKr (lightest line) by 10% increments. Spontaneous action potential ceased when relative activity of IKr was shifted by 80% (red line) or more toward late embryonic stage value. (D). Changes in action potential when relative activities of all currents except IK1 and IKr were shifted from early embryonic to late embryonic values by 10% increments

Mentions: The spontaneous action potential of early embryonic ventricular cells ceased when the relative activities of all current components were shifted by 10% or more toward the late embryonic stage value (Fig. 4A).Fig. 4


Simulation of developmental changes in action potentials with ventricular cell models.

Itoh H, Naito Y, Tomita M - Syst Synth Biol (2007)

Effects of shifting relative activities of all current components (A), IK1 (B), IKr (C), and of all current components except IK1 and IKr (D). (A) Changes in action potential when shifting relative activities of all currents by 10% increments. (B) Changes in action potential when shifting from relative activity of early embryonic IK1 (darkest line) to that of late embryonic IK1 (lightest line) by 10% increments. Spontaneous action potential ceased when relative activity of IK1 was shifted by 10% (red line) or more toward late embryonic stage value. Dataset could not be obtained when the current was shifted by 90% and 100% toward the late embryonic stage value, owing to collapse in the balance of the ionic concentration. (C) Changes in action potential when shifting from relative activity of early embryonic IKr (darkest line) to that of late embryonic IKr (lightest line) by 10% increments. Spontaneous action potential ceased when relative activity of IKr was shifted by 80% (red line) or more toward late embryonic stage value. (D). Changes in action potential when relative activities of all currents except IK1 and IKr were shifted from early embryonic to late embryonic values by 10% increments
© Copyright Policy
Related In: Results  -  Collection

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Fig4: Effects of shifting relative activities of all current components (A), IK1 (B), IKr (C), and of all current components except IK1 and IKr (D). (A) Changes in action potential when shifting relative activities of all currents by 10% increments. (B) Changes in action potential when shifting from relative activity of early embryonic IK1 (darkest line) to that of late embryonic IK1 (lightest line) by 10% increments. Spontaneous action potential ceased when relative activity of IK1 was shifted by 10% (red line) or more toward late embryonic stage value. Dataset could not be obtained when the current was shifted by 90% and 100% toward the late embryonic stage value, owing to collapse in the balance of the ionic concentration. (C) Changes in action potential when shifting from relative activity of early embryonic IKr (darkest line) to that of late embryonic IKr (lightest line) by 10% increments. Spontaneous action potential ceased when relative activity of IKr was shifted by 80% (red line) or more toward late embryonic stage value. (D). Changes in action potential when relative activities of all currents except IK1 and IKr were shifted from early embryonic to late embryonic values by 10% increments
Mentions: The spontaneous action potential of early embryonic ventricular cells ceased when the relative activities of all current components were shifted by 10% or more toward the late embryonic stage value (Fig. 4A).Fig. 4

Bottom Line: 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 Ca(2+) kinetics by relative activities.

View Article: PubMed Central - PubMed

Affiliation: Institute for Advanced Biosciences, Keio University, Fujisawa, Kanagawa, 252-8520, Japan, ducky@sfc.keio.ac.jp.

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) Ca(2+) 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 Ca(2+) kinetics by relative activities.

No MeSH data available.


Related in: MedlinePlus