Joseph Feher
The Use of Electronic Network Simulation Programs (SPICE) to Model Biological Systems

We have used the electronic network simulation program, SPICE, to simulate a variety of biological processes. Although originally designed to model electrical networks, the program can be applied to chemical and biological processes because of the similar form of the relationships between voltage, charge and capacitance and concentration, amount and volume. Here we describe its application to the transcellular transport of calcium across intestinal enterocytes. The biological transport mechanisms that were successfully modeled by SPICE include: (1) negative feed-back entry of calcium at the brush-border membrane of the intestine; (2) the binding of calcium to calbindin within the enterocyte cytoplasm; (3) diffusion of both free calcium and calcium bound to calbindin through the cytosol from the apical pole of the cell to its basolateral pole; and (4) saturable exit of calcium at the basolateral membrane. Here we present a description of the overall process of modeling using SPICE and how to encode biological variables into the program. Simulation of each transport mechanism in isolation allows the user to validate the simulation for those parts of the network for which an analytical solution is possible. The individual transport mechanisms were then assembled into a network which simulates calcium transport across the entire cell. The results of the simulation show that the calcium-binding protein, calbindin, can increase transport across all three sequential barriers to calcium by (1) reducing feed-back inhibition of calcium entry at the brush border; (2) enhancing diffusion through the cytosol; and (3) increasing efflux at the basolateral membrane by delivering more calcium to the starved basolateral calcium pump. The main advantage of SPICE is its relative simplicity. The structure of the SPICE network maps readily onto the structure of biological systems, which clarifies the SPICE network as an analogue of the biological system.

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