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Nicotinic Acetylcholine Receptor Kinetics of the Neuromuscular Junction Simulated Using SPICE – An Illustration of Physiological Process Simulation with Conventional Circuit Simulation Software

Abstract

With the advent of modern day computational power, there is a great deal of interest in the simulation and modeling of complex biological systems. A significant effort is being made to develop generalized software packages for the simulation of cellular processes, metabolic pathways and complex biochemical reaction systems. The advantages to being able to implement and simulate complex biological systems in a virtual environment are several. Simulations of this type, if sufficiently detailed, provide experimental physiologists with the ability to visualize the dynamics of a given biological system of interest. The validity of hypotheses related to the system under study can be tested in a virtual environment prior to carrying out experimental studies. We discuss a systematic approach by which certain reaction balance equations can be transformed into equivalent circuit models that may then be implemented and simulated using SPICE (Simulation Program with Integrated Circuit Emphasis). To introduce the methodology, we develop a simulation for a single ligand-receptor interaction and then we utilize this framework to implement a simulation of nicotinic acetylcholine receptor kinetics at the postsynaptic membrane of the neuromuscular junction. Although the example studies that we present are specific to biochemical reaction systems associated with cellular processes, the procedure is equally applicable to any biochemical or chemical process for which analogous systems of mass balance equations exist that have an equivalent circuit analog. The overall approach described above is useful from the biomedical engineering educational perspective because SPICE simulators are readily accessible to students in freeware versions that they can use to simulate and visualize relatively complex physiological processes such as neurotransmitter/receptor dynamics.

Introduction

During the past several years, there has been an increasing interest in the development of generalized software packages for simulating biological systems of varying complexity. Increasingly, experimental physiologists are relying on these software packages to assist with validation of empirical results. The public domain software packages NEURON and GENESIS are two good examples of simulation programs that are utilized with increasing frequency by experimental electrophysiologists .1,2 Other packages have been developed that focus on simulation of biochemical system dynamics 3 and still other tools, such as Bio-Spice, have been written for genetic circuit analysis but are being adapted to function as generic modeling and simulation environments.4 An excellent review of available software is provided by Takahashi et al. along with discussion of related software development issues.5

The use of virtual environments to simulate complex biological systems has advantages from the perspective of the ability to theoretically validate experimental results.6 Equally importantly, virtual studies provide physiologists with the opportunity to test hypotheses prior to undertaking experimental investigations which can be both expensive and time consuming.

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Szlavik, R. (2008, June), Nicotinic Acetylcholine Receptor Kinetics Of The Neuromuscular Junction Simulated Using Spice An Illustration Of Physiological Process Simulation With Conventional Circuit Simulation Software Paper presented at 2008 Annual Conference & Exposition, Pittsburgh, Pennsylvania. 10.18260/1-2--3819