Activation of rat recombinant α1β2γ2S GABAA receptor by the insecticide ivermectin

In the present study, the activation of rat recombinant alpha(1)beta(2)gamma(2s) gamma-aminobutyric acid (GABA)-ergic Cl- channel expressed in human embryonic kidney (HEK) 293 cells by ivermectin was investigated. Maximal activation of the channel occurred with GABA concentrations of 10 mM or 20 mu M ivermectin both achieving about the same current amplitudes. With those saturating concentrations, the currents rose with GABA within 1 ms to the maximal values, whereas the rise time for ivermectin was about 500 times longer. In contrast to activation with GABA, no desensitisation in the presence of the agonist was observed with ivermectin. With both agonists, two different open states were detected. On simultaneous application of GABA and ivermectin the current amplitudes and the kinetics were determined by the agonist applied in the concentration eliciting the higher open probability. It is concluded that GABA and ivermectin activated the channel independently resulting in different kinetic properties. (C) 2000 Elsevier Science B.V. All rights reserved.