Figure 7. Inhibition of cholesterol synthesis with mevastatin mimics acute depletion.

A and B, hypertonic sucrose stimulation after 6 h mevastatin treatment. A, sample traces. B, summary graph showing that the average charge transfer during the first 10 s of the 30 s sucrose response is decreased 80% after treatment with mevastatin for 6 h compared with non-treated cultures. The addition of cholesterol after mevastatin treatment rescued the depleted hypertonic sucrose responses to values not significantly different from non-treated cultures. Horizontal bar represents the presence of hypertonic sucrose. At least 2 cultures; no mevastatin, n = 7; mevastatin, n = 12; mevastatin + cholesterol, n = 3. C and D, field stimulation evoked responses after 6 h mevastatin treatment. C, sample traces. D, summary graph depicting a 70% reduction in the average evoked EPSC amplitude for cultures treated with mevastatin compared with non-treated neurones. The addition of cholesterol after mevastatin treatment rescued the reduced EPSC amplitudes to values not significantly different from non-treated cultures. Arrow represents timing of the stimulation. At least 2 cultures; no mevastatin, n = 5; mevastatin, n = 5; mevastatin + cholesterol, n = 4. E–G, mEPSCs after 6 h mevastatin treatment. E, sample traces. F, summary graph shows a 3-fold increase in the frequency of mEPSCs for cultures treated for 6 h with mevastatin compared with untreated neurones. The increased frequency was reduced to non-treated frequency levels after incubation with MCD: cholesterol complexes. G, the distributions of mEPSC amplitudes were not affected by these treatments as determined by the K-S test (P > 0.0001). At least 2 cultures; no mevastatin, n = 24; mevastatin, n = 13; mevastatin + cholesterol, n = 4. Error bars represent the s.e.m.*P < 0.05, **P < 0.01, ***P < 0.001.