A Novel Computational Model of Pacemaker Activity in the Mouse Atrioventricular Node Cell

Chiara Bartolucci1, Pietro Mesirca2, Clara Sales Belles3, Eugenio Ricci1, Eleonora Torre2, Julien Louraour2, Matteo Mangoni2, Stefano Severi1
1University of Bologna, 2Université de Monpellier, CNRS, INSERM, Montpellier, France, 3University of Barcellona


Nowadays many action potential (AP) models have been developed for most heart regions in a variety of species and cell types. Although, for the atrioventricular node (AVN), which acts as a subsidiary pacemaker and controls impulse conduction between atria and ventricle, there are few experimental data and its cellular electrophysiology properties are not completely understood. To date, only two models are available and were developed by Inada et al. for rabbit AVN cells and by Marger et al. for mice. Preliminary work, started by Marger et al., simulated the mouse AVN single-cell AP but did not contain subcellular compartments or the dynamics of intracellular ions’ concentrations. For these reasons, starting from the AVN model from Marger et al., we develop a new AVN model by introducing equations of calcium handling. The equations describing calcium handling are based on the AP mouse SAN model from Kharche’s work. The cell’s compartmentalization has been updated by including: the sarcoplasmic reticulum, divided into junctional and network spaces, the calcium subspace, and the cytosol. The current equations have been fitted with the experimental data available in the literature. With this updated model we have tested the blockade effects of some ionic currents involved in pacemaking. By blocking If of 50% or 90%, a slower rate is obtained followed by the arrest of cell beating under the condition of the almost total current block. The blockade of ICaD was important for AVN pacemaking since its blockade arrests automaticity. Finally, when IKr was reduced to half maximum conductance the cell slowed the beating and increasing the percentage of blocking the AP stops. In conclusion, our work proposes a new updated version of a mouse AVN single-cell AP and it reproduces almost all the AP hallmarks and can be used for simulating the effects of different currents blocks