Contribution of quantitative changes in individual ionic current systems to the embryonic development of ventricular myocytes

A simulation study

Chikako Okubo, Hitomi I. Sano, Yasuhiro Naito, Masaru Tomita

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Early embryonic rodent ventricular cells exhibit spontaneous action potential (AP), which disappears in later developmental stages. Here, we used 3 mathematical models - the Kyoto, Ten Tusscher-Panfilov, and Luo-Rudy models - to present an overview of the functional landscape of developmental changes in embryonic ventricular cells. We switched the relative current densities of 9 ionic components in the Kyoto model, and 160 of 512 representative combinations were predicted to result in regular spontaneous APs, in which the quantitative changes in Na+ current (I Na) and funny current (I f) made large contributions to a wide range of basic cycle lengths. In all three models, the increase in inward rectifier current (I K1) before the disappearance of I f was predicted to result in abnormally high intracellular Ca2+ concentrations. Thus, we demonstrated that the developmental changes in APs were well represented, as I Na increased before the disappearance of I f, followed by a 10-fold increase in I K1.

Original languageEnglish
Pages (from-to)355-367
Number of pages13
JournalJournal of Physiological Sciences
Volume63
Issue number5
DOIs
Publication statusPublished - 2013 Sep

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Muscle Cells
Embryonic Development
Specific Gravity
Action Potentials
Rodentia
Theoretical Models

Keywords

  • Cardiac ventricular cells
  • Computer simulation
  • Development
  • Electrophysiology
  • Ion channels
  • Spontaneous activity

ASJC Scopus subject areas

  • Physiology

Cite this

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abstract = "Early embryonic rodent ventricular cells exhibit spontaneous action potential (AP), which disappears in later developmental stages. Here, we used 3 mathematical models - the Kyoto, Ten Tusscher-Panfilov, and Luo-Rudy models - to present an overview of the functional landscape of developmental changes in embryonic ventricular cells. We switched the relative current densities of 9 ionic components in the Kyoto model, and 160 of 512 representative combinations were predicted to result in regular spontaneous APs, in which the quantitative changes in Na+ current (I Na) and funny current (I f) made large contributions to a wide range of basic cycle lengths. In all three models, the increase in inward rectifier current (I K1) before the disappearance of I f was predicted to result in abnormally high intracellular Ca2+ concentrations. Thus, we demonstrated that the developmental changes in APs were well represented, as I Na increased before the disappearance of I f, followed by a 10-fold increase in I K1.",
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AU - Sano, Hitomi I.

AU - Naito, Yasuhiro

AU - Tomita, Masaru

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