VOLTAGE-DEPENDENT UPTAKE IS A MAJOR DETERMINANT OF GLUTAMATE CONCENTRATION AT THE CONE SYNAPSE - AN ANALYTICAL STUDY

It was suggested that glutamate concentration at the synaptic terminal of the cones was controlled primarily by a voltage-dependent glutamat e transporter and that diffusion played a less important role. The con clusion was based on the observation that the rate of glutamate concen tration during the hyperpolarizing light response was dramatically slo wed when the transporter was blocked with dihydrokainate although diff usion remained intact. To test the validity of this notion we construc ted a model in which the balance among uptake, diffusion, and release determined the flow of glutamate into and out of the synaptic cleft. T he control of glutamate concentration was assumed here to be determine d by two relationships; 1)glutamate concentration is the integral over the synaptic volume of the rates of release, uptake, and diffusion, a nd 2) membrane potential is the integral over the membrane capacitance of the dark, leak, and transporter-gated chloride current. These rela tionships are interdependent because glutamate uptake via the transpor ter is voltage dependent and because the transporter-gated current is concentration dependent. The voltage and concentration dependence of r elease and uptake, as well as the light-elicited, transporter-gated, a nd leak currents were measured in other studies. All of these measurem ents were incorporated into our predictive model of glutamate uptake. Our results show a good quantitative fit between the predicted and the measured magnitudes and rates of change of glutamate concentration, d erived from the two interdependent relationships. This close fit suppo rts the validity of these two relationships as descriptors of the mech anisms underlying the control of glutamate concentration, it verifies the accuracy of the experimental data from which the functions used in these relationships were derived, and it lends further. support to th e notion that glutamate concentration is controlled primarily by uptak e at the transporter.