Computation of the Action Potential of a Cardiac Cell

2002 ◽  
pp. 74-117 ◽  
2016 ◽  
Vol 110 (3) ◽  
pp. 587a ◽  
Author(s):  
Ken Wang ◽  
Andreu Climent ◽  
David Gavaghan ◽  
Peter Kohl ◽  
Christian Bollensdorff

2017 ◽  
Vol 2017.23 (0) ◽  
pp. 1303
Author(s):  
Takashi OHYA ◽  
Tetsutaro KIKUCHI ◽  
Daisuke SASAKI ◽  
Tatsuya SHIMIZU ◽  
Kenjiro FUKUDA ◽  
...  

2019 ◽  
Author(s):  
Sam Coveney ◽  
Richard H. Clayton

AbstractCardiac cell models reconstruct the action potential and calcium dynamics of cardiac myocytes, and are becoming widely used research tools. These models are highly detailed, with many parameters in the equations that describe current flow through ion channels, pumps, and exchangers in the cell membrane, and so it is difficult to link changes in model inputs to model behaviours. The aim of the present study was to undertake sensitivity and uncertainty analysis of two models of the human atrial action potential. We used Gaussian processes to emulate the way that 11 features of the action potential and calcium transient produced by each model depended on a set of. The emulators were trained by maximising likelihood conditional on a set of design data, obtained from 300 model evaluations. For each model evaluation, the set of inputs was obtained from uniform distributions centred on the default values for each parameter, using latin-hypercube sampling. First order and total effect sensitivity indices were calculated for each combination of input and output. First order indices were well correlated with the square root of sensitivity indices obtained by partial least squares regression of the design data. The sensitivity indices highlighted a difference in the balance of inward and outward currents during the plateau phase of the action potential in each model, with the consequence that changes to one parameter can have opposite effects in the two models. Overall the interactions among inputs were not as important as the first order effects, indicating that model parameters tend to have independent effects on the model outputs. This study has shown that Gaussian process emulators are an effective tool for sensitivity and uncertainty analysis of cardiac cell models.Author summaryThe time course of the cardiac action potential is determined by the balance of inward and outward currents across the cell membrane, and these in turn depend on dynamic behaviour of ion channels, pumps and exchangers in the cell membrane. Cardiac cell models reconstruct the action potential by representing transmembrane current as a set of stiff and nonlinear ordinary differential equations. These models capture biophysical detail, but are complex and have large numbers of parameters, so cause and effect relationships are difficult to identify. In recent years there has been an increasing interest in uncertainty and variability in computational models, and a number of tools have been developed. In this study we have used one of these tools, Gaussian process emulators, to compare and contrast two models of the human atrial action potential. We obtained sensitivity indices based on the proportion of variance in a model output that is accounted for by variance in each of the model parameters. These sensitivity indices highlighted the model parameters that had the most influence on the model outputs, and provided a means to make a quantitative comparison between the models.


2018 ◽  
Vol 23 (3) ◽  
pp. 321-327 ◽  
Author(s):  
Takashi Ohya ◽  
Kazuki Nakazono ◽  
Tetsutaro Kikuchi ◽  
Daisuke Sasaki ◽  
Katsuhisa Sakaguchi ◽  
...  

2014 ◽  
Vol 7 (13) ◽  
Author(s):  
Alfredo Illanes Manríquez ◽  
Guillaume Sérandour

El presente trabajo tiene como objetivo principal relacionar la actividad eléctrica cardiaca celular con la actividad eléctrica cardiaca medida en una sola derivación del electrocardiograma (ECG), mediante un modelo paramétrico de potencial de acción (PA) celular, lo cual se llevó a cabo relacionando dinámicas conocidas, matemáticamente modelables, que existen a nivel de una célula cardiaca, a dinámicas que pueden ser encontradas en un registro ECG estándar. La principal dinámica celular a relacionar con el ECG es la conocida como curva de restitución celular en tres dimensiones, la cual relaciona la duración del potencial de acción celular (APD) con el intervalo diastólico que lo precede y con el mismo APD pero del ciclo cardiaco precedente. Curvas de restitución similares se encontraron en señales ECG registradas durante el test isométrico handgrip, relacionando el intervalo QT con el intervalo TQ que lo precede y con el intervalo QT del ciclo cardiaco precedente. Siguiendo esta similitud, un modelo paramétrico de curva de restitución, extraído de un modelo de PA a tres corrientes iónicas, es ajustado a la curva de restitución del ECG con el fin de estimar los parámetros del modelo de PA. Este modelo es finalmente simulado estimulándolo con un tren de impulsos de frecuencia igual a la frecuencia cardiaca del sujeto experimentado. Los resultados muestran que la curva de restitución obtenida experimentalmente a partir del ECG es similar a la obtenida a partir de la simulación del modelo de PA. Más aún, el APD simulado del modelo sigue de forma satisfactoria la variación en el tiempo del intervalo QT del sujeto experimentado. Esto abre nuevas perspectivas en el análisis de la actividad celular a partir de registros ECG estándar.Abstract: The main purpose of this paper is to relate cellular cardiac electrical activity with the cardiac electrical activity measured in only one electrocardiogram (ECG) lead, through a cellular action potential (AP) parametrical model. This is performed by relating known dynamics, which can be mathematically modeled, existing at a cardiac cell level, to dynamics which can be obtained from a standard ECG recording. The main cellular dynamic used for relating with the ECG is the one known as three dimensional cellular restitution curve, which relates the action potential duration (APD) with its preceding diastolic interval and with the APD of the preceding cardiac cycle. Similar restitution curves were found in ECG signals recorded under the isometric handgrip test by relating the QT interval with its preceding TQ interval and with the QT interval of the preceding cardiac cycle. Following this similarity, a parametrical restitution curve, derived from a three ionic current cellular AP model was fitted to the ECG restitution relation for AP model parameter estimation. This model is finally simulated by stimulating it with an impulse train of frequency similar to the heart rate of the tested subject. The results show that the restitution curve experimentally obtained from the ECG is similar to the one obtained from de AP model simulation. Moreover the simulated APD follows satisfactorily the QT interval time variation of the tested subject. This opens new perspectives for the analysis of cellular cardiac electrical activity from standard ECG recordings.


Author(s):  
Joachim R. Sommer ◽  
Teresa High ◽  
Betty Scherer ◽  
Isaiah Taylor ◽  
Rashid Nassar

We have developed a model that allows the quick-freezing at known time intervals following electrical field stimulation of a single, intact frog skeletal muscle fiber isolated by sharp dissection. The preparation is used for studying high resolution morphology by freeze-substitution and freeze-fracture and for electron probe x-ray microanlysis of sudden calcium displacement from intracellular stores in freeze-dried cryosections, all in the same fiber. We now show the feasibility and instrumentation of new methodology for stimulating a single, intact skeletal muscle fiber at a point resulting in the propagation of an action potential, followed by quick-freezing with sub-millisecond temporal resolution after electrical stimulation, followed by multiple sampling of the frozen muscle fiber for freeze-substitution, freeze-fracture (not shown) and cryosectionmg. This model, at once serving as its own control and obviating consideration of variances between different fibers, frogs etc., is useful to investigate structural and topochemical alterations occurring in the wake of an action potential.


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