Simulating the extrinsic regulation of the sinoatrial node cells using a unified computational model

Abstract

The aim of this work is to develop a computational model to study the extrinsic regulation of the heart rate variability (HRV) during sympathetic and/or vagal stimulation. The model here proposed is based on two recent models of the sinoatrial node cell (SANC) action potential and the influence of the autonomic nervous system (ANS) on the activity of ionic channels of SANCs. The HRV was simulated by applying a random frequency stimulation using both a normal and a beta probability density function (PDF) for different ranges of stimulation frequencies. The HRV was then analyzed by computing the scale exponent using detrended fluctuation analysis. We found that our model reproduces the value of the scale exponent observed in healthy humans (α=1.07± 0.05) when simultaneous vagal and sympathetic stimulus (with beta and normal PDFs, respectively) over the frequency range from 0 to 10 Hz are applied. Our model also predicts a Brownian motion behavior when the muscarinic receptors are blocked (α=1.8) and the white noise behavior when the b-adrenergic receptors are blocked (α=0.5). Our results shed light on how the ANS regulates the HRV in healthy conditions, where it is not enough to consider only one stimulation pathway with a simple normal PDF.

Parallel simulation of the synchronization of heterogeneous cells in the sinoatrial node

“…For decades, theoretical biophysicists have devoted themselves to the study of the electrical activity of single cells, being unable to develop models involving a large number of cells mainly due to computational limitations. The reason for this is that simulating the electrical activity of a single cell involves solving a large number of coupled differential equations to accurately describe the behavior of cell membrane proteins such as ionic channels, pumps, and exchangers . Furthermore, due to the importance of intracellular Ca 2+ for a myriad of cellular processes (including electrical activity itself), it is usually needed to include the intracellular distribution of Ca 2+ in the models, thus increasing considerably the number of differential equations .…”