Autonomic nervous system regulation of the sinoatrial cell depolarization rate: Unifying computational models

In the last years different computational models have been proposed to simulate the sinoatrial node cell (SANC) action potential. Also, there has been a great effort to model the heart regulation mechanism by the autonomic nervous system (ANS) through the sympathetic and parasympathetic pathways. Both computational models have tried to fit the rabbit and/or the guinea-pig experimental heart rate data with an increasing success. Thus, the aim of this work was to unify the available models that have been reported to study the heart rate behavior when the SANC is stimulated by using different frequency patterns. Our results contribute to the unification of part of the Scepanovic's model [1] (involved with second messengers dynamics and its influence over specific SANC ionic channels), and the SANC ionic channels computational model proposed by Severi et al. [2] in 2012. In this model unification we did refit some parameters, particularly, those related to the Hill functions in the dynamic modeling of phosphokinase and its effect on the ionic channels currents If and ICaL, and over the Pup, parameter that is related to the Ca(++) uptake by the sarcoplasmic reticulum. Also, we eliminated the neurotransmitter effect over the ionic current IKr that is not presented in the Severi's model. These modifications were enough to successfully reproduce the heart rate experimental recordings under acetylcholine (Ach) or norepinephrine (NE) for independent stimulation: Ach 10 nM stimulation showed a 21.54% action potential shift compared with the 20% reported for experimental recordings; Isoprenaline 1 μM, also displayed a depolarization increased rate of 29.3%, compared with the experimental data of 28.2%. Furthermore, we were able to reproduce the guinea-pig experimental heart rate recordings, when the SANC model was vagal stimulated by using a 2 Hz, 10 Hz and 20 Hz frequency for 10 seconds and the experimental heart rate data for a sympathetic stimulation of 10 Hz frequency for 10 seconds.