Computational Study of the Role of Funny Current in Atrioventricular Conduction by Multiscale Mouse Heart Models

Introduction: The funny current has a well-known role in pacemaking, but HCN4-KO mice experiments from Baruscotti et. Al. (2011) lead to hypothesise its necessary role also in AV conduction, since AV block and death occurred in mice. Using this experiment as rationale, this work aims to simulate ’in silico’ the AV node to gather knowledge about the AV conduction, and so check the consequence of funny current blocks. Materials and Methods: 1D and 2D simulations of the mouse AV node were performed using MATLAB® with increasing resolution: firstly atrial and AV cells were connected together, after the SA node was added, all in 1D. Going in 2D, the dual pathway conduction considered by simulating a standard configuration with insulated slow pathway (SP) and fast pathway (FP), but also a pseudo-anatomical schemes made of compact node (CN), inferior extension (INE) and CO (coronary sinus ostium) were tested. Results: The AV block didn’t occur in all the experiments. A slight conduction velocity change was detected in all the configurations. The SAN-paced configuration showed a decreasing rate during progressive If block, almost the 50% with 100% If block. The observed propagation along insulated SP and FP follows the textbook’s knowledge, with the FP capable of reaching the sink faster than the SP. The pseudo-anatomical configurations exhibited a complex conduction pattern, with no clear association between a location and the FP/SP. However, the slight conduction slowing associated with the If block was seen also here.