Developmental changes in the balance of glycolytic ATP production and oxidative phosphorylation in ventricular cells: A simulation study

Hitomi Sano, Tamami Toki, Yasuhiro Naito, Masaru Tomita

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


The developmental program of the heart requires accurate regulation to ensure continuous circulation and simultaneous cardiac morphogenesis, because any functional abnormalities may progress to congenital heart malformation. Notably, energy metabolism in fetal ventricular cells is regulated in a manner that differs from adult ventricular cells: fetal cardiomyocytes generally have immature mitochondria and fetal ventricular cells show greater dependence on glycolytic ATP production. However, although various characteristics of energy metabolism in fetal ventricular cells have been reported, to our knowledge, a quantitative description of the contributions of these factors to fetal ventricular cell functions has not yet been established. Here, we constructed a mathematical model to integrate various characteristics of fetal ventricular cells and predicted the contribution of each characteristic to the maintenance of intracellular ATP concentration and sarcomere contraction under anoxic conditions. Our simulation results demonstrated that higher glycogen content, higher hexokinase activity, and lower creatine concentration helped prolong the time for which ventricular cell contraction was maintained under anoxic conditions. The integrated model also enabled us to quantitatively assess the contributions of factors related to energy metabolism in ventricular cells. Because fetal cardiomyocytes exhibit similar energy metabolic profiles to stem cell-derived cardiomyocytes and those in the failing heart, an improved understanding of these fetal ventricular cells will contribute to a better comprehension of the processes in stem cell-derived cardiomyocytes or under pathological conditions.

Original languageEnglish
Pages (from-to)269-277
Number of pages9
JournalJournal of Theoretical Biology
Publication statusPublished - 2017 Apr 21


  • Anoxia
  • Creatine
  • Glycogen
  • Mitochondria
  • Oxidative phosphorylation

ASJC Scopus subject areas

  • Statistics and Probability
  • Modelling and Simulation
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Agricultural and Biological Sciences
  • Applied Mathematics


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