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. 2019 Jun 19;39(25):4909–4930. doi: 10.1523/JNEUROSCI.2226-18.2019

Figure 5.

Figure 5.

Y2Rs decrease tonic activation of PN GABABRs. A, Voltage-clamp (Vh = −55 mV) traces from a representative PN in control (black) and during application of the GABABR antagonist, CGP 52432 (1 μm; gray). The steady-state holding current was reduced by CGP 52432 in this cell, similar to actions of the Y2R agonist (compare Fig. 3). B, I–V plot of the KIR current blocked by 1 μm CGP 52432 (gray), which showed inward rectification and reversed at −92.2 ± 3.2 mV (two-way repeated-measures ANOVA; treatment: F(1,108) = 24.65, p < 0.0001; voltage: F(8,108) = 186.5, p < 0.0001; interaction: F(8,108) = 44.89, p < 0.0001; n = 13 cells, 11 rats). CGP 52432 significantly decreased the KIR as indicated (Bonferroni's post-test). C, I–V plots of the KIR blocked by [ahx5–24]NPY (1 μm) in the absence of other drugs (cells from D, E) (blue; n = 27, 20 rats) and in the presence (gray + blue) of CGP 52432 (1 μm; n = 12 cells, 9 rats; two-way ANOVA; treatment: F(1,333) = 3.280, p = 0.0710; voltage: F(8,333), p < 0.0001; interaction: F(8,333), p < 0.0001). In the presence of CGP 52432, [ahx5–24]NPY reduced significantly less current as indicated (Bonferroni's post-test). D, I–V plot of the KIR blocked by CGP 52432 (1 μm; gray) in the presence of TTX (500 nm), which reversed at −104.5 ± 3.5 mV (two-way repeated-measures ANOVA; treatment: F(1,36) = 7.204, p = 0.0109; voltage: F(8,36) = 70.95, p < 0.0001; interaction: F(8,36) = 6.440, p < 0.0001; n = 5 cells, 4 rats). CGP 52432 continued to significantly decrease the KIR in the presence of TTX as indicated (Bonferroni's post-test). E, I–V plots of the KIR blocked by [ahx5–24]NPY (1 μm) in TTX (500 nm), in the absence (blue; n = 8 cells, 6 rats) or presence of CGP 52432 (1 μm) (blue + gray; n = 6 cells, 4 rats; two-way ANOVA; treatment: F(1,108) = 13.61, p = 0.0004; voltage: F(8,104) = 5.956, p < 0.0001; interaction: F(8,108) = 1.944, p = 0.0606). With CGP and TTX both present, [ahx5–24]NPY was significantly less effective than in TTX alone as indicated (Bonferroni's post-test). *p < 0.05, **p < 0.01, ***p < 0.001.