Activation of Cl- channels by avermectin in rat cultured hippocampal neurons.
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 microM and a Hill coefficient 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 microM) substantially but transiently reduced the AVM response. Outside-out 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.
Schönrock
B
B
Max-Planck-Institut für Hirnforschung, Frankfurt, Germany.
Bormann
J
J
D000818:Animals; D000831:Animals, Newborn; D000871:Anthelmintics / Q000494:pharmacology*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects*; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010852:Picrotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects; D054830:Sesterterpenes
D000871:Anthelmintics; D018118:Chloride Channels; D007559:Ivermectin; D010852:Picrotoxin; D011963:Receptors, GABA-A; D054830:Sesterterpenes; C019264:avermectin; C022961:picrotoxinin