Development of a Sex-Specific Action Potential Model for Rabbit Atrial Cells

This work presents an analysis of a mathematical model of action potentials (APs) in rabbit atrial cells, with a focus on gender differences. Gender medicine is increasingly recognized as essential, highlighting how sex and hormones influence the symptomatology and treatment of diseases. In particular, we focused on sex differences using a rabbit animal model. We adapted a previously proposed ionic model of rabbit atrial electrophysiology. A sensitivity analysis (SA) using Sobol’ indices was performed to identify the ionic conductances that most influence the properties of the AP. We employed a Gaussian Process emulator, significantly decreasing the computational time required for the SA while maintaining high accuracy. Parameter optimization successfully reproduced experimental APs. Finally, we used Approximate Bayesian Computation with Sequential Monte Carlo methods (SMC-ABC) to estimate model parameters and quantify uncertainties, revealing varying degrees of parameter identifiability. Results showed that AP duration is primarily affected by L-type calcium conductance, while I<inf>K1</inf> and the Na - K pump influenced the resting membrane potential. We observed statistically significant sex differences in the I–V curve for I<inf>K1</inf>, but differences in conductances were not significant, possibly due to the limited sample size.