NITONIC ACETYLCHOLINE RECEPTOR INTERACTIONS

Biochemical tools used to study nitonic acetylcholine receptor interactions

Biochemical tools used to study nitonic acetylcholine receptor interactions

Introduction

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 these tools are related to the system under study can be tested in a virtual environment prior to carrying out experimental studies. Over here, discussed 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 tools, I have developed 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 I 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 tool that can use to simulate and visualize relatively complex physiological processes such as neurotransmitter/receptor dynamics.

Discussion and Analysis

The two important tools that will be discussed consist of a simple ligand-receptor interaction neglecting endocytosis adapted from Fogler et al.14 Based on the methodology illustrated, the framework associated with the first example will be used to develop a model of the reaction kinetics of nicotinic acetylcholine receptors at the postsynaptic membrane of the neuromuscular junction (Bertram, 2006, Pp. 56-58).

Ligand-Receptor Interaction

Figure 1 is a diagram of a simple ligand-receptor interaction where the rate constants kf (M1s-1) and kr (s-1) model the reaction associated with the ligand binding to the receptor and the reverse dissociation reaction respectively.The associated equilibrium reaction and the concomitant reaction rate equation are shown in 1 where R is the number of unoccupied receptors per cell, L is the free ligand concentration (M/dm3) and C is the number of bound receptor ligand complexes per cell.

(1)

The total number of receptors per cell RT is equal to the number of free receptors and the number of receptors associated with bound receptor ligand complexes C such that RT = R + C. The values of the rate constants and species concentrations are shown in Table 1.

Development of a SPICE equivalent circuit model proceeds directly from the form of (1). If we multiply the ordinary differential equation in (1) by a dummy capacitance value Cd then the ...