Effects of avermectin B1a (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 GABA 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 pmoll−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 pmoll−1 AVM could be fitted by a single exponential (τ=3.3ms). For a higher AVM concentration (1 pmoll−1) two exponentials (τ1 = 0.5ms, τ2 = 2.4ms) were needed to fit the distribution. A similar effect was elicited by decreasing the extracellular Ca2+ concentration from 13.5 to 1 mmoll−1 during the application of 0.1 pmoll−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 multitransmitter-gated chloride channel in this preparation. Binding sites for the drug are discussed.
Effect of quisqualic acid on the excitatory junctional potential in the crayfish opener muscle.