Figure 2.
Interleukin-6 decreases synaptic balance between inhibition and excitation. (A) Synaptic current-voltage (I–V) relationship obtained mediating 10eIPSCs in the presence of the glutamate receptor blockers 6,7-Dinitroquinoxaline-2,3-dione (DNQX) (10 μmol/L) and kynurenate (KYN) (2 mmol/L). The reversal potential for γ-aminobutyric acid-A receptor (GABAAR)-mediated currents (VGABA = −64 ± 2 mV, n = 3) is close to the Cl- Nernst potential calculated theoretically (VCl− = −65 mV). The insert displays the inversion of inhibitory synaptic currents. (B) Effect of SR-95531 (gabazine) application on the amplitude of the signal recorded at Vh = +10 mV, confirming the GABAergic nature of the synaptic response. (C) The I–V relationship in the presence of the GABAAR and N-methyl-D-aspartate receptor (NMDAR) blockers gabazine and kynurenic acid. Synaptic currents display rectification probably due to the presence of unchelated polyamines (n = 3). The insert displays some of the traces. (D) The DNQX blocks synaptic currents at Vh = −65 mV, confirming the glutamatergic nature of the synaptic response. (E) Representative traces (above) and sketch of the holding potential Vh corresponding to the experiment in (F). Scale bars are calibrated as in the rightmost trace. (F) After identification of the proper stimulation site and intensity, producing a reliable eEPSC and eIPSC, a baseline of eEPSC was recorded at Vh = −65 mV for 15 or more min (red triangles on the left). After depolarization to Vh = + 10 mV, a baseline of synaptic responses (eIPSCs, blue circles) was recorded before application of IL-6 (10 ng/mL), which lasted for the whole remainder of the experiment. After stabilization of the eIPSC, amplitude was shifted back to Vh = −65 mV to monitor possible changes in eEPSC (red triangles on the right). Numbers 1–4 in (E) correspond to traces in 1–4 in (F). Traces were obtained by averaging 10 consecutive events. (G) The IL-6 decreases the ratio between inhibitory and excitatory synaptic amplitudes (synaptic inhibition/excitation ratio ≡ AIPSC/AEPSC) without changing glutamatergic responses (**p < .02) (H) but only affecting inhibition (I) (n = 7; ***p < .002). AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; other abbreviations as in Figure 1.