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. © American Society for Engineering Education, 2008.