TY - JOUR
T1 - Contribution of quantitative changes in individual ionic current systems to the embryonic development of ventricular myocytes
T2 - A simulation study
AU - Okubo, Chikako
AU - Sano, Hitomi I.
AU - Naito, Yasuhiro
AU - Tomita, Masaru
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
KW - Cardiac ventricular cells
KW - Computer simulation
KW - Development
KW - Electrophysiology
KW - Ion channels
KW - Spontaneous activity
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U2 - 10.1007/s12576-013-0271-x
DO - 10.1007/s12576-013-0271-x
M3 - Article
C2 - 23760774
AN - SCOPUS:84890309315
VL - 63
SP - 355
EP - 367
JO - Journal of Physiological Sciences
JF - Journal of Physiological Sciences
SN - 1880-6546
IS - 5
ER -