A Model for Zebrafish Ventricular Tissue

Ludovica Cestariolo1, Marina Bataller Martinez2, Jose M Ferrero3, Jose F Rodriguez Matas1
1Politecnico di Milano, 2Universidad Politecnica de Valencia, 3Ci2B, Universitat Politecnica de Valencia


Abstract

In recent years, interest in zebrafish has significantly grown thanks to its electrophysiological characteristics which make it very similar to humans. The common aspects are numerous. In particular, the zebrafish shows an action potential much closer to those of humans than other mammals generally considered. This similarity is related to the presence of ~71% of human genes orthologues that lead to a functional similarity in cardiac ion channels. Thus, zebrafish is increasingly proposed as a model for pharmacological and genetic screening. This work develops a detailed action potential model for the zebrafish by considering the main ionic channels and currents involved. The Ten Tusscher (TT) model has been reparametrized to adapt it to the zebrafish. The currents considered for the model are: fast Na+ current INa (Figure), slow delayed rectifier current IKs, rapid delayed rectifier current IKr, inward rectifier K+ current IK1, L-type Ca2+ current ICaL, T-type Ca2+ current ICaT (introduced as new in the model), the Na+/K+ pump and the Na+/Ca2+ exchanger. Instead, the transient outward current Ito was not considered since no evidence regarding its presence in the zebrafish was found in literature. The model well describes the experimental data present for most of the current showing an increase in the time constants (around 7 times slower for the sodium and slow rectifying potassium current) consistent with the lower temperature associated with the physiological function of the Zebrafish (23° C against 37° C for humans). The model describes the four phases of the AP model with an upstroke of 7 mV/ms and an action potential duration of 230 ms, both in the range of experimental values.