Avermectin B1a irreversibly blocks postsynaptic potentials at the lobster neuromuscular junction by reducing muscle membrane resistance.

Abstract

Avermectin B1a, a macrocyclic lactone [from Streptomyces avermitilis] with broad spectrum anthelmintic activity, affects neuromuscular transmission in the lobster [Homarus americanus] stretcher muscle. Perfusion of the muscle with 1-10 .mu.g/ml eliminates inhibitory postsynaptic potentials within a few minutes. Intracellularly recorded excitatory postsynaptic potentials are gradually reduced in amplitude over 20-30 min, and their falling phases become faster; there is no effect on extracellularly recorded excitatory potentials. Avermectin B1a reduces the input resistance of the muscle fibers with a time course similar to that of the reduction of excitatory potentials. Washing for up to 2 h with drug-free solution fails to reverse the drug''s effects. Perfusion with 20 .mu.g of picrotoxin/ml results in recovery of the excitatory potentials and input resistance. Avermectin B1a also blocks the firing of the crayfish [Procambarus clarkii] stretch receptor neuron, and this block is also reversed by picrotoxin. The reduction in excitatory postsynaptic potentials after avermectin B1a treatment may be caused solely by reduction in membrane resistance. The reduction in membrane resistance may be due to the the opening of membrane Cl- channels, perhaps including those regulated by GABA at the inhibitory synapse.