Figure 2.

Glu uptake-induced reversal of glial GABA transporters contributes to tonic inhibition of neurons during enhanced network activity. Left, holding currents from representative experiments plotted at 1 s intervals during control condition (black), SNAP-5114 application (red) and washout (blue) with Gaussian fits to the histograms of the holding current recorded during each condition. Right, voltage clamp recording segments (V_h = 0 mV) low-pass filtered at 1 kHz from the same experiments showed at left. (A) Effect of GAT-2/3 blockade by 100 μM SNAP-5114 on the holding current in [Mg²⁺] = 1,800 μM buffer. (B) Effect of GAT-2/3 blockade by 100 μM SNAP-5114 on the holding current in [Mg²⁺] = 10 μM buffer. (C) Effect of GAT-2/3 blockade by 100 μM SNAP-5114 on the holding current in [Mg²⁺] = 1 μM buffer in the presence of the non-transportable Glu uptake blocker DHK (100 μM). Average holding current: 88.5 ± 26.4 pA in the presence of 100 μM DHK vs. 93.6 ± 27.2 pA in the presence of 100 μM DHK and 100 μM SNAP-5114, P = 0.31, N = 8 cells/5 animals. (D) Effect of GAT-2/3 blockade by 100 μM SNAP-5114 on the holding current in [Mg²⁺] = 10 μM buffer in the presence of 100 μM picrotoxin. Average holding current: 9.3 ± 15.6 pA in control vs. 7.5 ± 12.7 pA in the presence of 100 μM SNAP-5114, P = 0.58, N = 4 cells/2 animals.