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M. J. Rowan, W. Shen; Transient Light-Adaptation Enhances Cone Signaling by Suppression of Excitatory Amino Acid Transporter II (EAAT2). Invest. Ophthalmol. Vis. Sci. 2010;51(13):4796.
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© ARVO (1962-2015); The Authors (2016-present)
Purposes: Previously, we demonstrated that EAAT2 activity in cone terminals is necessary to reduce the synaptic strength of 2nd -order neurons in dark. This study explored a novel regulation of cone EAAT2 activity via transient light adaptation, resulting in enhanced cone signaling to 2nd -order neurons. In addition, the underlying mechanism of this transporter regulation was uncovered.
Whole cell patch clamp was performed on cones in dark- and transiently light-adapted retinal slices. Endogenous and exogenous EAAT currents were generated in cones with either a paired-pulse depolarization or with 1mM glutamate, respectively. DHKA and TBOA were used to inhibit EAAT2 currents and overall EAAT currents, respectively. Network inputs were always blocked with PTX and Strychnine or with Cd2+. NEM was applied to arrest G-protein signaling as necessary. Slices were light adapted with strong, red light for 1 to 5 minutes.
In dark adapted slices, exogenous application of 1mM glutamate elicited a large, sustained current in cones that was partially blocked by DHKA and fully blocked by TBOA. After light exposure, EAAT currents were inhibited approximately 35%; the remaining current was DHKA-insensitive, indicating that light strongly suppressed EAAT2 activity. Endogenous EAAT currents were observed from cones after paired-pulse depolarization; the DHKA-sensitive portion was similarly inhibited following light adaptation. This inhibition was reversed with NEM application and persisted in the presence of Cd2+, indicating that an intracellular G-protein sensitive pathway was involved. In addition, transient light adaptation enhanced the cone-driven light off-set responses in 2nd-order neurons, which mimicked the effect of DHKA in dark conditions previously described.
We determined that transient light adaptation suppressed EAAT2 uptake activity in cone terminals, leading to enhanced glutamatergic transmission to 2nd -order neurons. We hypothesize that a translocation of transducin, which initiates a G-protein related intracellular cascade, to the cone terminal may lead to cone EAAT2 inhibition following light exposure.
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