Mathematical modeling is a valuable tool to help understanding physiological phenomena, such as the cardiac contraction. Among these models, the electrophysiological model of mouse ventricular myocyte developed by Morotti et al. in 2014. In the present study, a more recent version of the electrophysiological model of Morotti model, in conjunction with the Negroni model, was used to investigate the impact of changes in the association (kon) and dissociation (koff) rate constants of Ca2+ at troponin C (TnC) on the Ca2+ transients and the contraction force of the concurrent twitches. The sensitivity of the cardiomyocyte contractile apparatus to cytosolic Ca2+. The timecourses of the cytosolic Ca2+ concentration ([Ca2+]i) and of contraction force evoked by an current pulse were simulated using basal kon and koff values obtained from the literature (control), as well as values modified by a factor of 3 (test). The relationship between tonic force and the negative logarithm of molar Ca2+ concentration (pCa) was also simulated under control and test conditions. Increase in twitch contraction force and reduced in Ca2+ transient amplitude and leftward shift in the force vs. pCa curve were observed by kinetic changes that increased TnC affinity for Ca2+, while the opposite was seen for decreased affinity. It is concluded that the qualitative changes reduced resulting from alteration of the kinetics of TnC-Ca2+ interaction do not depend on the electrophysiological model used.

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Study on the Effect of Changing Myofilament Sensitivity to Ca2+ During Twitches Evoked Using the Morotti Model of Cardiomyocyte Electrophysiology

  • Matheus Leonardo Alves de Camargo,
  • G. G. Silva,
  • J. W. M. Bassani,
  • R. A. Bassani,
  • D. Sato,
  • R. R. Silva

摘要

Mathematical modeling is a valuable tool to help understanding physiological phenomena, such as the cardiac contraction. Among these models, the electrophysiological model of mouse ventricular myocyte developed by Morotti et al. in 2014. In the present study, a more recent version of the electrophysiological model of Morotti model, in conjunction with the Negroni model, was used to investigate the impact of changes in the association (kon) and dissociation (koff) rate constants of Ca2+ at troponin C (TnC) on the Ca2+ transients and the contraction force of the concurrent twitches. The sensitivity of the cardiomyocyte contractile apparatus to cytosolic Ca2+. The timecourses of the cytosolic Ca2+ concentration ([Ca2+]i) and of contraction force evoked by an current pulse were simulated using basal kon and koff values obtained from the literature (control), as well as values modified by a factor of 3 (test). The relationship between tonic force and the negative logarithm of molar Ca2+ concentration (pCa) was also simulated under control and test conditions. Increase in twitch contraction force and reduced in Ca2+ transient amplitude and leftward shift in the force vs. pCa curve were observed by kinetic changes that increased TnC affinity for Ca2+, while the opposite was seen for decreased affinity. It is concluded that the qualitative changes reduced resulting from alteration of the kinetics of TnC-Ca2+ interaction do not depend on the electrophysiological model used.