Cone photoreceptors respond to their own glutamate release in the tiger salamander.

Abstract

Pulse-like currents resembling miniature postsynaptic currents were recorded in patch-clamped isolated cones from the tiger salamander retina. The events were absent in isolated cones without synaptic terminals. The frequency ofevents was increased by either raising the osmotic pressure or depolarizing the cell. It was decreased by the application of either glutamate or the glutamate-transport blockers dihydrokainate and D,L-threo-3-hydroxyaspartate. The events required external Na+ for which Li' could not substitute. The reversal potential of these currents followed the equilibrium potential for Cl-when internal Cl-concentration was changed. Thus, these miniature currents appear to represent the presynaptic activation of the glutamate receptor with glutamate transporter-like pharmacology, caused by the photoreceptor's own vesicular glutamate release. Using a noninvasive method to preserve the intracellular Cl-concentration, we showed that glutamate elicits an outward current in isolated cones. Fluorescence of the membrane-permeable form of fura-2 was used to monitor Ca2+ entry at the cone terminal as a measure of membrane depolarization. The increase in intracellular Ca2+ concentration, elicited by puff application of 30 mM KCI, was completely suppressed in the presence of 100 ,iM glutamate. Puff application of glutamate alone had no measurable depolarizing effect. These results suggest that the equilibrium potential for Cl1, Ecl, was more negative than the activation range for Ca2+ channels and that glutamate elicited an outward current, hyperpolarizing the cones.

The Glutamate-Activated Anion Conductance in Excitatory Amino Acid Transporters Is Gated Independently by the Individual Subunits

“…The activation of EAAT subtypes with large anion conductances has been suggested to directly influence the excitability of presynaptic terminals in certain neurons (Picaud et al, 1995a;Palmer et al, 2003;Veruki et al, 2006;Wersinger et al, 2006). The effect that the EAAT-mediated anion current has on the excitability of the terminal depends not only on the glutamate affinity and on the relative conductance of the anion channel but also on the shape of the glutamate concentration dependence, i.e., whether the anion channel is activated cooperatively or independently by the individual subunits (Fig.…”

“…Although it is activated by glutamate, this anion conductance is thermodynamically uncoupled from glutamate uptake, and thus glutamate uptake is unaffected by anion concentrations (Wadiche et al, 1995a). Although the role of the anion conductance in EAATs is unclear, it has been postulated that EAAT subtypes with particularly high anion permeability may contribute directly to excitability in certain cells (Picaud et al, 1995a;Palmer et al, 2003;Veruki et al, 2006;Wersinger et al, 2006).…”

D2-like dopamine receptors promote interactions between calcium and chloride channels that diminish rod synaptic transfer in the salamander retina

“…Another possibility is that quinpirole might stimulate other Cl − currents. The major Cl − current described in photoreceptors is I Cl(Ca) , but Cl − transporter currents also have been described (Eliasof & Werblin, 1993;Picaud et al, 1995, Larsson et al, 1996Fan & Yazulla, 1997) and other Cl − channels may be present, since a ClC-2 antibody labels the ONL and OPL and a ClC-3 antibody labels the OPL (Enz et al, 1999;Stobrawa et al, 2001). Cl − flux through these channels might regulate I Ca activity in a manner analogous to the proposed regulation by I Cl(Ca) .…”

“…It is possible, however, that a similar interaction between I Ca and I Cl(Ca) might also operate in cones since both conductances are present (Maricq & Korenbrot, 1988;Barnes & Hille, 1989;Yagi & MacLeish, 1994). In cones, estimates of E Cl range from −65 to at or slightly above the dark resting potential (Kaneko & Tachibana, 1986;Thoreson & Burkhardt, 1991;Picaud et al, 1995. If E Cl is negative to the resting potential, activation of I Cl(Ca) would hyperpolarize the cell and thus limit regenerative activation of Ca 2+ channels (Maricq & Korenbrot, 1988;Yagi & MacLeish, 1994).…”

Sulfhydryl modification of V449C in the glutamate transporter EAAT1 abolishes substrate transport but not the substrate-gated anion conductance

“…One proposed role for the conductance is to dampen cell excitability, thus preventing a decrease in the transporter turnover rate that occurs with depolarization. In salamander cone cells, which express EAAT5, the chloride conductance may act as a feedback sensor to limit depolarization and thus additional glutamate release (12), whereas in retinal bipolar cells it appears to mediate part of the light response (13).…”