A Tridomain Model for Potassium Clearance in Optic Nerve of Necturus

Abstract

The accumulation of potassium in the narrow space outside nerve cells is a classical subject of biophysics that has received much attention recently. It may be involved in potassium accumulation \textcolor{black}{including} spreading depression, perhaps migraine and some kinds of epilepsy, even (speculatively) learning. Quantitative analysis is likely to help evaluate the role of potassium clearance from the extracellular space after a train of action potentials. Clearance involves three structures that extend down the length of the nerve: glia, extracellular space, and axon and so need to be described as systems distributed in space in the tradition used for electrical potential in the `cable equations' of nerve since the work of Hodgkin in 1937. A three-compartment model is proposed here for the optic nerve and is used to study the accumulation of potassium and its clearance. The model allows the convection, diffusion, and electrical migration of water and ions. We depend on the data of Orkand et al to ensure the relevance of our model and align its parameters with the anatomy and properties of membranes, channels, and transporters: our model fits their experimental data quite well. The aligned model shows that glia has an important role in buffering potassium, as expected. The model shows that potassium is cleared mostly by convective flow through the syncytia of glia driven by osmotic pressure differences. A simplified model might be possible, but it must involve flow down the length of the optic nerve. It is easy for compartment models to neglect this flow. Our model can be used for structures quite different from the optic nerve that might have different distributions of channels and transporters in its three compartments. It can be generalized to include a fourth (distributed) compartment representing blood vessels to deal with the glymphatic flow into the circulatory system.