{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T01:58:29Z","timestamp":1785463109641,"version":"3.56.0"},"reference-count":41,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T00:00:00Z","timestamp":1726185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T00:00:00Z","timestamp":1726185600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["TNE FANTASY 19CV03"],"award-info":[{"award-number":["TNE FANTASY 19CV03"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,10]]},"abstract":"\n Abstract<\/jats:title>\n \n 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 We recalibrated and validated the model against existing and unpublished experimental data.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\u00a0=\u00a0175\u00a0bpm, experimental range [121, 191]\u00a0bpm). Notably, our study sheds light on the contribution of L\u2010type calcium currents, through both Ca\n v<\/jats:sub>\n 1.2 and Ca\n v<\/jats:sub>\n 1.3 channels, in AVN cells. The model replicates several experimental observations, including the cessation of firing upon block of Ca\n v<\/jats:sub>\n 1.3 or\n I<\/jats:italic>\n Na,r<\/jats:sub>\n current.\n I<\/jats:italic>\n f<\/jats:sub>\n 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.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n This paper introduces a comprehensive computational model of mouse atrioventricular node (AVN) cell action potentials (APs).<\/jats:p>\n <\/jats:list-item>\n \n Our model is based on the electrophysiological data from isolated mouse AVN cells and exhibits an action potential and calcium transient that closely match the experimental records.<\/jats:p>\n <\/jats:list-item>\n \n \n By simulating the effects of blocking specific ionic currents, the model effectively predicts the roles of L\u2010type Ca\n v<\/jats:sub>\n 1.2 and Ca\n v<\/jats:sub>\n 1.3 channels, T\u2010type calcium channels, sodium currents (TTX\u2010sensitive and TTX\u2010resistant), and the funny current (\n I<\/jats:italic>\n f<\/jats:sub>\n ) in AVN pacemaking.\n <\/jats:p>\n <\/jats:list-item>\n \n \n The study also emphasizes the significance of other ionic currents, including\n I<\/jats:italic>\n Kr<\/jats:sub>\n ,\n I<\/jats:italic>\n to<\/jats:sub>\n ,\n I<\/jats:italic>\n Kur<\/jats:sub>\n , in regulating AP characteristics and cycle length in AVN cells.\n <\/jats:p>\n <\/jats:list-item>\n \n The model faithfully reproduces the rate dependence of action potentials under pacing, opening the possibility of use in impulse propagation models.<\/jats:p>\n <\/jats:list-item>\n \n The population\u2010of\u2010models approach showed the robustness of this new AP model in simulating a wide spectrum of cellular pacemaking in AVN.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n 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