An In-Silico Study of the Effects of Conductance Variation on the Regionally Based Action Potential Morphology.

2019 ◽  
Author(s):  
Jordan Elliott ◽  
Olaf Doessel ◽  
Axel Loewe ◽  
Luca Mainardi ◽  
Valentina Corino ◽  
...  
Keyword(s):  
Action Potential ◽  
In Silico ◽  
In Silico Study

scholarly journals Individual Contributions of Cardiac Ion Channels on Atrial Repolarization and Reentrant Waves: A Multiscale In-Silico Study

2022 ◽  
Vol 9 (1) ◽  
pp. 28
Author(s):  
Henry Sutanto
Keyword(s):  
Ion Channels ◽  
Action Potential ◽  
In Silico ◽  
Computational Study ◽  
Surrogate Marker ◽  
Cardiac Ion Channels ◽  
Atrial Electrophysiology ◽  
In Silico Study ◽  
In Silico Models ◽  
Atrial Repolarization

The excitation, contraction, and relaxation of an atrial cardiomyocyte are maintained by the activation and inactivation of numerous cardiac ion channels. Their collaborative efforts cause time-dependent changes of membrane potential, generating an action potential (AP), which is a surrogate marker of atrial arrhythmias. Recently, computational models of atrial electrophysiology emerged as a modality to investigate arrhythmia mechanisms and to predict the outcome of antiarrhythmic therapies. However, the individual contribution of atrial ion channels on atrial action potential and reentrant arrhythmia is not yet fully understood. Thus, in this multiscale in-silico study, perturbations of individual atrial ionic currents (INa, Ito, ICaL, IKur, IKr, IKs, IK1, INCX and INaK) in two in-silico models of human atrial cardiomyocyte (i.e., Courtemanche-1998 and Grandi-2011) were performed at both cellular and tissue levels. The results show that the inhibition of ICaL and INCX resulted in AP shortening, while the inhibition of IKur, IKr, IKs, IK1 and INaK prolonged AP duration (APD). Particularly, in-silico perturbations (inhibition and upregulation) of IKr and IKs only minorly affected atrial repolarization in the Grandi model. In contrast, in the Courtemanche model, the inhibition of IKr and IKs significantly prolonged APD and vice versa. Additionally, a 50% reduction of Ito density abbreviated APD in the Courtemanche model, while the same perturbation prolonged APD in the Grandi model. Similarly, a strong model dependence was also observed at tissue scale, with an observable IK1-mediated reentry stabilizing effect in the Courtemanche model but not in the Grandi atrial model. Moreover, the Grandi model was highly sensitive to a change on intracellular Ca2+ concentration, promoting a repolarization failure in ICaL upregulation above 150% and facilitating reentrant spiral waves stabilization by ICaL inhibition. Finally, by incorporating the previously published atrial fibrillation (AF)-associated ionic remodeling in the Courtemanche atrial model, in-silico modeling revealed the antiarrhythmic effect of IKr inhibition in both acute and chronic settings. Overall, our multiscale computational study highlights the strong model-dependent effects of ionic perturbations which could affect the model’s accuracy, interpretability, and prediction. This observation also suggests the need for a careful selection of in-silico models of atrial electrophysiology to achieve specific research aims.

scholarly journals Lead and Carbon Monoxide Effects on Human Atrial Action Potential. In Silico Study

2017 ◽  
Author(s):  
Catalina Tobon ◽  
Diana C Pachajoa ◽  
Juan P Ugarte ◽  
Andres Orozco-Duque ◽  
Javier Saiz
Keyword(s):  
Carbon Monoxide ◽  
Action Potential ◽  
In Silico ◽  
In Silico Study

scholarly journals Sulfur Dioxide Effects on Human Atrial Action Potential. In Silico Study

2018 ◽  
Author(s):  
Laura C Palacio ◽  
Geraldine Durango ◽  
Juan P Ugarte ◽  
Javier Saiz ◽  
Catalina Tobon
Keyword(s):  
Sulfur Dioxide ◽  
Action Potential ◽  
In Silico ◽  
In Silico Study

In Silico Study of Structural and Geometrical Requirements of Natural Sesquiterpene Lactones with Trypanocidal Activity

2013 ◽  
Vol 13 (10) ◽  
pp. 1407-1414 ◽  
Author(s):  
L. Fabian ◽  
V. Sulsen ◽  
F. Frank ◽  
S. Cazorla ◽  
E. Malchiodi ◽  
...  
Keyword(s):  
In Silico ◽  
Sesquiterpene Lactones ◽  
Trypanocidal Activity ◽  
In Silico Study
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