ACTIVATION OF CL- CHANNELS BY AVERMECTIN IN RAT CULTURED HIPPOCAMPAL-NEURONS

The actions of the insecticide avermectin (AVM) were studied in rat cu ltured hippocampal neurons with patch-clamp techniques. Application of micromolar concentrations of AVM to voltage-clamped cells gave rise t o whole-cell currents, which showed a slow time-course of activation i n the order of 10 s, and wash-out periods of typically 20 min. Dose-re sponse curves revealed a half-maximally activating AVM concentration ( EC50) Of 2.0+/-0.6 muM and a Hill coefficent of 1.5+/-0.9. The current activated by AVM was carried predominantly by Cl- ions, as demonstrat ed by ion-substitution experiments. The Cl- channel blocker picrotoxin in (100 muM) substantially but transiently reduced the AVM response. O utside-out patch recording showed that AVM opened Cl- channels with a conductance of 40+/-12 pS. The open-time distribution was characterize d by two time constants of 11 ms and 259 ms. It is suggested that AVM directly activates Cl- channels in mammalian central neurons, which re semble the channels activated by the physiological transmitters GABA a nd glycine.