Towards the Development of an in Silico Model for the Zebrafish Action Potential

Ludovica Cestariolo1, Jose M Ferrero2, Zachary Long3, T Quinn3, Jose F Rodriguez Matas1
1Politecnico di Milano, 2Ci2B, Universitat Politecnica de Valencia, 3Dalhousie University


Abstract

In the last decades, the use of zebrafish in different fields has significantly grown. This increasing interest is related to its characteristics, which make it very similar to humans in many aspects, especially a similar electrophysiology owing large percentage of orthologues of human genes. Thus, zebrafish has been proposed as a pharmacological and genetic screening model. Developing a numerical AP model seems very important to study pathologies and drug administration to understand the ionic mechanisms involved. Thanks to this knowledge, reducing the number of animals used for experimental studies will also be possible. This work represents the first approach toward the development of a numerical model for the adult zebrafish AP. The developed model uses the TP04 formulation of the action potential for human cardiomyocytes as a base model. Starting from this model, the main currents have been reparametrized to adapt them to the zebrafish while extending the model to account for the T-type calcium current present in the zebrafish and deleting the Ito current, which is not found to be present instead. Moreover, AP recordings from the ventricle of adult zebrafish in isolated hearts were collected to validate the numerical model. Preliminary results showed an AP morphology in good agreement with experimental data and correct restitution curves behaviors.