B. Roska et al., VOLTAGE-DEPENDENT UPTAKE IS A MAJOR DETERMINANT OF GLUTAMATE CONCENTRATION AT THE CONE SYNAPSE - AN ANALYTICAL STUDY, Journal of neurophysiology, 80(4), 1998, pp. 1951-1960
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.