Computer model of membrane current and intracellular Ca2+ flux in the isolated guinea pig ventricular myocyte

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Abstract

This paper presents the equations and responses of a mathematical model that simulates the transmembrane current and intracellular concentrations of Ca2+ ([Ca2+]), Na+ ([Na+]), and K+ ([K+]) of an isolated guinea pig myocyte. The structure of the model is closely related to the formulation of DiFrancesco and Noble (9). Quantitative values are based on a large number of experimental constraints, taken from the literature on isolated myocytes as well as our own experimental studies, that describe the properties of individual channels and integrated responses of whole cells under a variety of conditions. The model was constructed as a homeostatic system. The equilibrium of the model corresponds to the resting potential and intracellular ionic concentrations of unstimulated myocytes. The model generates deviations from equilibrium corresponding to the behavior of cells after stimulation of action potentials at different rates, blockade of Na-K- adenosinetriphosphatase (ATPase), reduction in extracellular [K+], and injection of constant depolarizing current. Simulations from the model suggest that changes in myoplasmic [Ca2+] at different stimulation rates, the generation of restitution and postextrasystolic potentiation, and the development of intracellular [Ca2+] oscillations arise simply from different interactions between uptake of Ca2+ into the sarcoplasmic reticulum via the Ca2+-ATPase, Ca2+-induced Ca2+ release of Ca2+ into the myoplasm, flux between regions of uptake and release, and leakage between sarcoplasmic reticulum and myoplasm. The model also demonstrates that a wide variety of basic electrophysiological responses of the isolated guinea pig myocyte can be simulated with quantitative precision by a single set of equations based on experimentally measured transmembrane current and intracellular [Ca2+] and [Na+].

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume265
Issue number6 34-6
StatePublished - 1993

Fingerprint

Intracellular Membranes
computer simulation
Computer Simulation
guinea pigs
myocytes
Muscle Cells
Guinea Pigs
calcium
Sarcoplasmic Reticulum
Adenosine Triphosphatases
sarcoplasmic reticulum
Membrane Potentials
Action Potentials
Theoretical Models
adenosinetriphosphatase
Injections
uptake mechanisms
action potentials
membrane potential
oscillation

Keywords

  • intracellular calcium concentration
  • isolated myocytes

ASJC Scopus subject areas

  • Physiology
  • Agricultural and Biological Sciences(all)

Cite this

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abstract = "This paper presents the equations and responses of a mathematical model that simulates the transmembrane current and intracellular concentrations of Ca2+ ([Ca2+]), Na+ ([Na+]), and K+ ([K+]) of an isolated guinea pig myocyte. The structure of the model is closely related to the formulation of DiFrancesco and Noble (9). Quantitative values are based on a large number of experimental constraints, taken from the literature on isolated myocytes as well as our own experimental studies, that describe the properties of individual channels and integrated responses of whole cells under a variety of conditions. The model was constructed as a homeostatic system. The equilibrium of the model corresponds to the resting potential and intracellular ionic concentrations of unstimulated myocytes. The model generates deviations from equilibrium corresponding to the behavior of cells after stimulation of action potentials at different rates, blockade of Na-K- adenosinetriphosphatase (ATPase), reduction in extracellular [K+], and injection of constant depolarizing current. Simulations from the model suggest that changes in myoplasmic [Ca2+] at different stimulation rates, the generation of restitution and postextrasystolic potentiation, and the development of intracellular [Ca2+] oscillations arise simply from different interactions between uptake of Ca2+ into the sarcoplasmic reticulum via the Ca2+-ATPase, Ca2+-induced Ca2+ release of Ca2+ into the myoplasm, flux between regions of uptake and release, and leakage between sarcoplasmic reticulum and myoplasm. The model also demonstrates that a wide variety of basic electrophysiological responses of the isolated guinea pig myocyte can be simulated with quantitative precision by a single set of equations based on experimentally measured transmembrane current and intracellular [Ca2+] and [Na+].",
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AB - This paper presents the equations and responses of a mathematical model that simulates the transmembrane current and intracellular concentrations of Ca2+ ([Ca2+]), Na+ ([Na+]), and K+ ([K+]) of an isolated guinea pig myocyte. The structure of the model is closely related to the formulation of DiFrancesco and Noble (9). Quantitative values are based on a large number of experimental constraints, taken from the literature on isolated myocytes as well as our own experimental studies, that describe the properties of individual channels and integrated responses of whole cells under a variety of conditions. The model was constructed as a homeostatic system. The equilibrium of the model corresponds to the resting potential and intracellular ionic concentrations of unstimulated myocytes. The model generates deviations from equilibrium corresponding to the behavior of cells after stimulation of action potentials at different rates, blockade of Na-K- adenosinetriphosphatase (ATPase), reduction in extracellular [K+], and injection of constant depolarizing current. Simulations from the model suggest that changes in myoplasmic [Ca2+] at different stimulation rates, the generation of restitution and postextrasystolic potentiation, and the development of intracellular [Ca2+] oscillations arise simply from different interactions between uptake of Ca2+ into the sarcoplasmic reticulum via the Ca2+-ATPase, Ca2+-induced Ca2+ release of Ca2+ into the myoplasm, flux between regions of uptake and release, and leakage between sarcoplasmic reticulum and myoplasm. The model also demonstrates that a wide variety of basic electrophysiological responses of the isolated guinea pig myocyte can be simulated with quantitative precision by a single set of equations based on experimentally measured transmembrane current and intracellular [Ca2+] and [Na+].

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