The insecticide avermectin b (la) activates a chloride channel in crayfish muscle membrane.

Effects of avermectin Bl a (AVM) have been tested on excised outside-out or inside-out patches of crayfish stomach muscle membrane. Continuous supervision of AVM (0.1-1 pmoll (-1)) to the outside-out patches induced openings of channels(22 pS) which were similar in conductance and kinetics to the chloride channels activated by glutamate, quisqualic acid, ibotenic acid and nicotinic agonists,whereas GAB A mainly activated a second, larger conductance state (44 pS). This effect was reversible. AVM did not activate the excitatory, glutamate-activated cation channel. Upon raising the AVM-concentration to 10 pmol1(-1) and above, an enormous increase in the rate of openings of channels (22 pS) occurred. This effect could not be washed out during the lifetime of the patch. Using inside-out patches,it was shown that the single-channel current amplitude, for both the reversible and irreversible drug actions, strongly depended on intracellular chloride concentration.Applied to the sarcoplasmic side of inside-out patches, AVM did not activate any channel. The distribution of open times for 0-1 pmol1(-1) AVM could be fitted by a single exponential ((tau)=3-3 ms). For a higher AVM concentration(1 pmol1(-1)) two exponentials ((tau)(1) = 0-5 ms, (tau)(2) = 2-4 ms) were needed to fit the distribution. A similar effect was elicited by decreasing the extracellular Ca2(+)concentration from 13-5 to 1 mmol1(-1) during the application of 0.1 pmol1(-1) AVM.Picrotoxin blocked the activation of chloride channels for both the reversible and irreversible effects of AVM. It is suggested that AVM activates the multi transmitter-gated chloride channel in this preparation. Binding sites for the drug are discussed.