Resonant model-A new paradigm for modeling an action potential of biological cells.

Sucheta Sehgal,Avinash Malik,Nitish D Patel,Partha S Roop,Mark L Trew

doi:10.1371/journal.pone.0216999

Abstract

Organ level simulation of bioelectric behavior in the body benefits from flexible and efficient models of cellular membrane potential. These computational organ and cell models can be used to study the impact of pharmaceutical drugs, test hypotheses, assess risk and for closed-loop validation of medical devices. To move closer to the real-time requirements of this modeling a new flexible Fourier based general membrane potential model, called as a Resonant model, is developed that is computationally inexpensive. The new model accurately reproduces non-linear potential morphologies for a variety of cell types. Specifically, the method is used to model human and rabbit sinoatrial node, human ventricular myocyte and squid giant axon electrophysiology. The Resonant models are validated with experimental data and with other published models. Dynamic changes in biological conditions are modeled with changing model coefficients and this approach enables ionic channel alterations to be captured. The Resonant model is used to simulate entrainment between competing sinoatrial node cells. These models can be easily implemented in low-cost digital hardware and an alternative, resource-efficient implementations of sine and cosine functions are presented and it is shown that a Fourier term is produced with two additions and a binary shift.

Highlights

Computer models of electrical function in excitable cells can be used to conduct pharmaceutical drug testing, assess the risk of adverse health outcomes, plan treatments and do basic science investigations [1]
The adjusted R squared value of this action potential (AP) waveshape generated by resonant model (RM) with eight oscillators is 0.9929, which means that it captured more than 99% of the variability of the reference AP waveshape data
We have proposed a new modeling technique called as a Resonant model (RM) to describe the electrical behavior of biological cells observed in vivo or in vitro via simplified in silico representation of their action potential morphology

Summary

Introduction

Computer models of electrical function in excitable cells can be used to conduct pharmaceutical drug testing, assess the risk of adverse health outcomes, plan treatments and do basic science investigations [1]. The goal is to parameterize models such that organ-level patientspecific behaviors can be studied [2]. An emerging application is toward functional and formal validation of medical devices [3]. At the core of organ models are cellular membrane models describing the electrophysiology of constituent excitable cells. Many of these cell models are traced to the pioneering work of Hodgkin and Huxley [4] that quantified ion currents and the action potential of nerve axons. Many detailed electrophysiology models [2, 5, 6], reduced electrophysiology

Results

Discussion

Conclusion