Modeling And Simulation Of Ventricular Myocytes Coupled With Mitochondrial Mechanisms

Myocardial cell simulation modeling has become a research hotspot in recent years.Because the integrated model of ventricular myocyte will contribute to study the excitation-contraction coupling mode of cardio-myocytes under normal and pathological conditions,the physiological and pathological mechanisms of myocardial cells can be further explored to assist the clinical diagnosis of macroscopic diseases,establishing an complete model of ventricular myocyte has became the trend in this field.However,it is a difficult and complicated research work to establish an complete model of ventricular myocyte,by integrating thermology,dynamics,electrophysiology and other characteristics.As an important organelle in cardiomyocytes,mitochondrial supplies energy with ATP.It affects metabolism and cardiac bioenergetic signaling.Especially during exercise,mitochondrial maintains steady-state cytoplasmic Ca2+([Ca2+]i)and cellular metabolism,playing a role in the complex process of life activity.Since mitochondria plays a role in myocardial cell movement and pathological state,the establishment of an integrated mitochondrial coupling mechanism of myocardial cell model can be used as a supplementary means for the study of cardiac movement conditions,myocardial ischemia,coronary heart disease and other pathological diagnosis.In this paper,we presented an integrated mathematical model of myocardial cell which couples the epicardial ten Tusscher model(TNNP)with the model of mitochondrial energy generation.Here,based on experimantal data of cellular enzymes and their substrates concentrations,we simulated the electrophysiological properties of myocardial cell under the nonnal and exercise conditions,recapitulating the effect of Ca2+ on energy exchange between mitochondrial and cytoplasm.In conclusion,this model verified that mitochondrial supplies energy by the Ca2+handling.Under exercise condition,the concentration of[Ca2+],rises,inducing calcium overloads,the mitochondrial maintains homeostasis by recycling Ca2+,however,heavier exercise weakens the ability of recycling.Additionally,the results show that mitochondrial has little effect on L-type calcium current(ICaL),The higher the intense,that is,the higher the stimulation frequency was,the larger the amplitude of ICaL in the integrated model was,the shorter the APD and platform duration was.The effects on Ca2+ indicate the importance of mitochondria in the modeling and simulation of myocardial cells.The research work of this thesis is of great significance to further understand the mechanisms underlying cardiac mitochondrial.