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. 2008 Nov 7;283(45):31005–31011. doi: 10.1074/jbc.M804464200

FIGURE 4.

FIGURE 4.

RSDP selectively impairs GABAB(1a,2) receptors located at glutamatergic terminals. A, the percentage of mEPSC and mIPSC frequency inhibition by baclofen (bac, 100 μm) and adenosine (adeno, 100 μm) under control condition (ACSF, white bars) and after incubation of acute hippocampal slices from wild-type (WT) mice with RSDP (40 nm, black bars) for 6 h. Baclofen was significantly less efficient in reducing the frequency of mEPSCs recorded from CA1 pyramidal neurons incubated with RSDP than from neurons incubated with ACSF (ACSF, 71.0 ± 5.4% inhibition, n = 5; RSDP, 7.6 ± 2.2% inhibition, n = 9; ***, p < 0.001, Kolmogorov-Smirnov; see also supplemental Table S2). RSDP was without effect on adenosine-mediated mEPSC frequency inhibition (ACSF, 67.0 ± 5.3% inhibition, n = 5; RSDP, 76.0 ± 3.0% inhibition, n = 9; supplemental Table S2). As an additional control, RSDP was also without effect on the baseline mEPSC frequency or amplitude (for values, see supplemental Table S3). RSDP did not affect the baclofen- or adenosinemediated inhibition of the mIPSCs frequency recorded from CA1 pyramidal neurons (for values, see supplemental Table S2). RSDP did not alter the amplitudes of Kir3 current responses induced by baclofen and adenosine in CA1 pyramidal neurons (n = 6 per condition). B, RSDP impairs the baclofen-mediated mEPSC frequency inhibition in 1b-/- mice (ACSF, 67.0 ± 3.0% inhibition; RSDP, 6.0 ± 2.0%; n = 4; ***, p < 0.001, Kolmogorov-Smirnov). Incubation with RSDP had no effect on baclofen- or adenosine-mediated effects on the mIPSC frequency (for values, see supplemental Table S2) or on Kir3 current amplitudes. Baclofen-induced Kir3 current responses were reduced in the 1b-/- when compared with wild-type mice, as described (22). C, baclofen failed to depress the mEPSCs frequency in 1a-/- mice due to the lack of GABAB heteroreceptors in these mice (22). The basal mEPSC frequency in 1a-/- mice was increased (for values, see supplemental Table S3), as reported previously (22). RSDP was without effect on the baclofen- or adenosine-mediated inhibition of the mIPSC frequency (for values, see supplemental Table S2) or on Kir3 currents in 1a-/- mice. All values are means ± S.E.