Figure 7

Paclitaxel reduces glial glutamate transporter activities through activating TLR4. (A): An astrocyte in the mouse spinal dorsal horn was stained by the astrocyte specific dye, sulforhodomine 101 (SR101, 100 μM) (top). (B): Inward and outward currents (top) in a spinal astrocyte were evoked by voltage steps (10 mV/step) from −130 mV to +70 mV (bottom), indicating a passive membrane property of astrocytes. (C): Astrocytes identified by this way all (8 cells) expressed GFAP. N: Negative control. GAPDH was used as internal control. GTCs were evoked by L-glutamate (50 μM) injected onto the astrocyte through a puff-electrode (A, bottom). Such currents were almost abolished in the presence of the specific glial glutamate transporter blocker TFB-TBOA (10 μM) (D). Bath-perfusion of paclitaxel (1 ng/ml) significantly reduced GTC amplitudes and charge transfers (E), and these effects were abolished in the presence of the TLR4 antagonist LPS-RS (2 μg/ml) (F). (G): GTCs recorded from spinal slices obtained from TLR4 knockout mice were not altered by bath-perfusion of paclitaxel (1 ng/ml). Bar graphs show the mean (+S.E.) GTC amplitude and charge transfer before (baseline), during and after washout of the tested agent(s). Number of animals included in each group for the analysis is shown in each bar. ***P < 0.001; NS, no statistical significance.