Computational modelling of mouse atrio ventricular node action potential and automaticity

Bartolucci, Chiara ; Mesirca, Pietro ; Ricci, Eugenio ; Sales-Bellés, Clara (Universidad de Zaragoza) ; Torre, Eleonora ; Louradour, Julien ; Mangoni, Matteo Elia ; Severi, Stefano

Resumen: The atrioventricular node (AVN) is a crucial component of the cardiac conduction system. Despite its pivotal role in regulating the transmission of electrical signals between atria and ventricles, a comprehensive understanding of the cellular electrophysiological mechanisms governing AVN function has remained elusive. This paper presents a detailed computational model of mouse AVN cell action potential (AP). Our model builds upon previous work and introduces several key refinements, including accurate representation of membrane currents and exchangers, calcium handling, cellular compartmentalization, dynamic update of intracellular ion concentrations, and calcium buffering. We recalibrated and validated the model against existing and unpublished experimental data. In control conditions, our model reproduces the AVN AP experimental features, (e.g. rate = 175 bpm, experimental range [121, 191] bpm). Notably, our study sheds light on the contribution of L-type calcium currents, through both Cav1.2 and Cav1.3 channels, in AVN cells. The model replicates several experimental observations, including the cessation of firing upon block of Cav1.3 or INa,r current. If block induces a reduction in beating rate of 11%. In summary, this work presents a comprehensive computational model of mouse AVN cell AP, offering a valuable tool for investigating pacemaking mechanisms and simulating the impact of ionic current blockades. By integrating calcium handling and refining formulation of ionic currents, our model advances understanding of this critical component of the cardiac conduction system, providing a platform for future developments in cardiac electrophysiology.

Idioma: Inglés

DOI: 10.1113/JP285950

Año: 2024

Publicado en: JOURNAL OF PHYSIOLOGY-LONDON 602, 19 (2024), 4821-4847
ISSN: 0022-3751

Tipo y forma: Article (Published version)

Área (Departamento): Área Teoría Señal y Comunicac. (Dpto. Ingeniería Electrón.Com.)