Summary
The actions of the insecticide avermectin (AVM) were studied in rat cultured hippocampal neurons with patch-clamp techniques. Application of micromolar concentrations of AVM to voltage-clamped cells gave rise to whole-cell currents, which showed a slow time-course of activation in the order of 10 s, and wash-out periods of typically 20 min. Dose-response curves revealed a half-maximally activating AVM concentration (EC50) of 2.0±0.6 μM and a Hill coefficent of 1.5±0.9. The current activated by AVM was carried predominantly by Cl− ions, as demonstrated by ion-substitution experiments. The Cl− channel blocker picrotoxinin (100 μM) substantially but transiently reduced the AVM response. Outsideout patch recording showed that AVM opened Cl− channels with a conductance of 40±12 pS. The open-time distribution was characterized by two time constants of 11 ms and 259 ms. It is suggested that AVM directly activates Cl− channels in mammalian central neurons, which resemble the channels activated by the physiological transmitters GABA and glycine.
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Correspondence to: J. Bormann at the above address
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Schönrock, B., Bormann, J. Activation of Cl− channels by avermectin in rat cultured hippocampal neurons. Naunyn-Schmiedeberg's Arch Pharmacol 348, 628–632 (1993). https://doi.org/10.1007/BF00167239
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DOI: https://doi.org/10.1007/BF00167239