Analyzing an electrogenic cotransporter.

A model for the sodium-dependent accumulation of glutamate by synaptosomes has been presented which fits the data of Wheeler and his coworkers and supports their hypothesis of an electrogenic cotransporter. Since their hypothesis was based on experimental data on the operation of the cotransporter on the outer membrane, the model was expanded to predict events when the cotransporter was operating on both sides of the membrane. The model predicts that the accumulation of glutamate is sensitive to the synaptosomal sodium and emphasizes the importance of the sodium/potassium pump to maintain this value. A model which uses only an electrogenic form of the cotransporter on the external membrane and a neutral form on the inside of the membrane predicts too much or too little accumulation of glutamate at different membrane potentials. A model which uses an electrogenic cotransporter on the external membrane and a concentration-dependent sodium glutamate leak would require a significant increase in the permeability of sodium glutamate when the membrane depolarizes. Only the operation of all four mentioned mechanisms will fit experimental data at two different external sodium concentrations and over the range of membrane potentials measured experimentally.