Effect of avermectin B1a on chick neuronal gamma-aminobutyrate receptor channels expressed in Xenopus oocytes.

Chick brain mRNA was isolated and injected into Xenopus oocytes. This led to the expression of gamma-aminobutyrate (GABA) channels easily accessible for current measurements using the voltage clamp technique. The effect of the anthelmintic natural product avermectin B1a on the GABA current was studied quantitatively. In the presence of the drug, GABA-induced chloride currents were strongly enhanced in a dose-dependent manner. Half-maximal stimulation of the current evoked by 5 microM GABA was found with about 0.1 microM avermectin B1a. Avermectin B1a did not affect the reversal potential of the current or the maximal response elicited by GABA, and did not alter the membrane permeability in the absence of GABA. The major effects of avermectin B1a were a shift of the Ka for GABA from 21 microM to 2 microM, and a decrease of the apparent Hill coefficient for GABA from 1.7 to 1.1. Furthermore, in the presence of avermectin B1a, desensitization of the GABA current was strongly inhibited. The benzodiazepine-binding site ligand Ro 15-1788 did not affect the action of avermectin B1a if present at concentrations up to 1 microM. The stimulatory effects of the drug were additive to the ones by the barbiturate pentobarbital, if both agents were added at low concentrations. At higher concentrations each of these agents inhibited the stimulatory effects of the other.