Electrodiffusive model for astrocytic and neuronal ion concentration dynamics.

ABSTRACT

The cable equation is a proper framework for modeling electrical neural signalling that takes place at a timescale at which the ionic concentrations vary little. However, in neural tissue there are also key dynamic processes that occur at longer timescales. For example, endured periods of intense neural signaling may cause the local extracellular K(+)-concentration to increase by several millimolars. The clearance of this excess K(+) depends partly on diffusion in the extracellular space, partly on local uptake by astrocytes, and partly on intracellular transport (spatial buffering) within astrocytes. These processes, that take place at the time scale of seconds, demand a mathematical description able to account for the spatiotemporal variations in ion concentrations as well as the subsequent effects of these variations on the membrane potential. Here, we present a general electrodiffusive formalism for modeling of ion concentration dynamics in a one-dimensional geometry, including both the intra- and extracellular domains. Based on the Nernst-Planck equations, this formalism ensures that the membrane potential and ion concentrations are in consistency, it ensures global particle/charge conservation and it accounts for diffusion and concentration dependent variations in resistivity. We apply the formalism to a model of astrocytes exchanging ions with the extracellular space. The simulations show that K(+)-removal from high-concentration regions is driven by a local depolarization of the astrocyte membrane, which concertedly (i) increases the local astrocytic uptake of K(+), (ii) suppresses extracellular transport of K(+), (iii) increases axial transport of K(+) within astrocytes, and (iv) facilitates astrocytic relase of K(+) in regions where the extracellular concentration is low. Together, these mechanisms seem to provide a robust regulatory scheme for shielding the extracellular space from excess K(+).