A general approach to modeling conduction and concentration dynamics in excitable cells of concentric cylindrical...

This paper discusses mathematical approaches for modeling the propagation of the action potential and ion concentration dynamics in a general class of excitable cells and cell assemblies of concentric cylindrical geometry. Examples include myelinated and unmyelinated axons, single strands of interconnected cardiac cells and outer hair cells. A key feature in some of the cells is the presence of a small working volume such as the periaxonal space between the myelin sheath and the axon in the myelinated axon and the extracisternal space between the plasma membrane and the subsurface cisterna of the outer hair cell. Proper treatment of these cell types requires a modeling approach which can readily address these anatomical properties and the non-uniform biophysical properties of the concentric membranes and the ionic composition of the volumes between the membranes. An electrodiffusion approach is first developed in which the Nernst-Planck equation is used to characterize axial ion fluxes. It is then demonstrated that this "full" model can be stepwise reduced, eventually becoming equivalent to the standard cable equation formulation. This is done in a manner that permits direct comparisons between the full and simplified models by running simulations using a single parameter set. An intermediate approach where the contributions of the axial currents to ion concentration changes and the effect of varying ion concentrations on solution conductivities are ignored is derived and is found adequate in many cases. Two application examples are given: a "cardiac strand" model, for which the intermediate formulation is shown sufficient and a model of the myelinated axon, for which the full electrodiffusion formulation is clearly necessary. The latter finding is due to spatial inhomogeneities in the anatomy and distribution of ion channels and transporters in the myelinated axon and the restricted periaxonal space between the myelin sheath and the axon.