A general model and computer simulation of ionic signaling and chemical transport in cells

This thesis describes a generalized model of cellular electrochemical dynamics, the numerical methods for computer simulation of the model and results of a computer program developed to implement the simulation. The developmental philosophy of this project was to provide a flexible blueprint under which the researcher could construct a comprehensive and sophisticated simulation of cell excitability and transport utilizing well understood and theoretically rigorous principles. The model considers membrane conductance, transport properties, and gating currents as well as chemical concentration dynamics inside and outside the cell. Space clamp conditions are assumed, meaning that voltage and concentration gradients along the membrane are ignored. Different models of transmembrane electrodiffusion are considered such as those described by parallel conductances, Goldman-Hodgkin-Katz constant field theory or Eyring rate theory. Gating of ion channels and transport of ions are described by multi-state kinetic models. Intracellular concentration dynamics due to diffusion, buffering, and membrane fluxes are followed. Extracellular concentration dynamics are also considered. Finally an integration method for stiff systems (Gear method) is provided so that kinetic systems involving rates of state transitions that differ by many orders of magnitude can be considered. With the exception of extracellular concentration dynamics the model is based on biophysical principles rather than empirical functions.