Figure 5. Effects of cyclosporin A and CGP-37157 on kainate responses.

Example traces from individual fura-2 AM-loaded cells. Cells were stimulated with 200 μM kainate for 90 s (open bars), then left to recover. Incubation with CysA or CGP-37157 was as indicated by filled bars. A, successive stimulations with kainate evoked slowly rising elevations of [Ca²⁺]_i in an O-2A cell, which declined slowly after removal of the agonist. Pretreatment for 60 s with 5 μM CysA did not significantly alter the kainate-evoked response. B, successive stimulations with kainate evoked an elevation of [Ca²⁺]_i which declined slowly after removal of the agonist. Pretreatment with 25 μM CGP-37157 for 60 s markedly reduced the amplitude of the response. C, experimental design is as shown in B. A proportion of O-2A cells was found in which CGP-37157 pretreatment did not significantly diminish the amplitude of the kainate-evoked [Ca²⁺]_i response. In these cells, a second effect of this agent can be seen, as the rate of decline of the response after removal of agonist was markedly accelerated. D, CGP-37157 was applied in this experiment for 90 s immediately after removal of kainate. The rate of return to basal levels was increased by CGP-37157 treatment compared with that found in the control responses. E, kainate evoked large elevations of [Ca²⁺]_i in oligodendrocytes as well as in O-2A cells. CGP-37157 was found to increase the rate of return of kainate-evoked [Ca²⁺]_i responses to basal levels in many cells. CGP-37157 was also found to decrease kainate response amplitude in a proportion of oligodendrocytes (see Fig. 6).