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A dynamic model of the mammalian ventricular action potential: Formulation and physiological simulations

Luo, Ching-Hsing
http://rave.ohiolink.edu/etdc/view?acc_num=case1060102425

Abstract Details

1991, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
The model is based, whenever possible, on recent single-cell and single-channel experiments in cardiac myocytes. The development of the model is divided into two phases. The first phase updates the fast sodium current ( INa), time-independent potassium current ( IK1), and time-dependent potassium current ( IK). It also includes a plateau potassium current ( IKp), a background current ( Ib) and the possibility of changing extracellular potassium concentration (K) o. The fast sodium current, INa, is characterized by fast upstroke velocity ( .Vmax=400 V/sec) and slow recovery from inactivation. The time-independent potassium current, IK1, includes a negative-slope phase and displays significant cross-over phenomenon between I-V curves as (K) o is varied. The time-dependent potassium current, IK, shows only a minimal degree of cross-over. The phase-1 model described above focuses on processes of depolarization and repolarization and the underlying sodium and potassium membrane currents; the slow inward current is adopted, without change, from the Beeler-Reuter model and provides the current necessary to maintain the plateau of the action potential. The phase-1 model is based completely on membrane ionic channels and does not incorporate other processes such as electrogenic ionic pumps and exchangers. Moreover, it does not account for processes that regulate intracellular calcium concentration and determine its dynamics and the resulting calcium transients during the action potential. The phase-2 model, in addition to updating the calcium current ( ICa), incorporates the sodium-potassium pump ( INaK), a sarcolemmal calcium pump ( Ip(Ca)), the sodium-calcium exchanger ( INaCa), a nonspecific calcium-activated current ( Ins(Ca)), calcium buffers inside the cell volume and the processes of uptake and release of calcium by the sarcoplasmic reticulum. The phase-2 model is very complex, but it simulates correctly the dynamic concentration changes of the various ions during the action potential and the effects of these changes on the electrical activity of the cell. It also accounts for longer term concentration changes and can be used to simulate long term effects of various abnormal situations such as metabolic inhibition of the sodium-potassium pump. This ability to incorporate dynamic changes differentiates the phase-2 model from the phase-1 model. Since the model simulates correctly dynamic changes in intracellular calcium, it provides the basis for the development of models of excitation-contraction coupling in cardiac muscle. (Abstract shortened with permission of author.)
Yoram Rudy (Advisor)
538 p.
Engineering, Biomedical
Mammalian ventricular action potential

Recommended Citations

Citations

  • Luo, C.-H. (1991). A dynamic model of the mammalian ventricular action potential: Formulation and physiological simulations [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1060102425

    APA Style (7th edition)

  • Luo, Ching-Hsing. A dynamic model of the mammalian ventricular action potential: Formulation and physiological simulations. 1991. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1060102425.

    MLA Style (8th edition)

  • Luo, Ching-Hsing. "A dynamic model of the mammalian ventricular action potential: Formulation and physiological simulations." Doctoral dissertation, Case Western Reserve University, 1991. http://rave.ohiolink.edu/etdc/view?acc_num=case1060102425

    Chicago Manual of Style (17th edition)

case1060102425
1,514
© 1991, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.