Actions of dihydroavermectin B1a on insect muscle

Muscle bundle 33 of the locust (Schistocerca gregaria) extensor tibiae muscle which is sensitive to gamma-aminobutyric acid (GABA) and receives inhibitory innervation, exhibited both reversible and irreversible responses to dihydroavermectin B1a (DHAVM). These responses involved increases in C1- permeability. DHAVM (0.000075-0.0075 microgram ml-1) induced reversible dose-dependent increases in C1- permeability and partially blocked GABA-induced C1- conductance. These effects appear to be due to an interaction of DHAVM with the GABA receptor-C1- ion channel complex. DHAVM (0.01-1.0 microgram ml-1) induced an irreversible increase in C1- conductance which continued to rise after DHAVM application was stopped. At these concentrations DHAVM potentiated GABA-induced C1- conductances which were in turn reduced by microperfusion of DHAVM (0.01-1.0 microgram ml-1) during bath application of GABA. DHAVM (0.0001-1.0 microgram ml-1) induced only irreversible increases in C1- conductance when applied to fast muscle bundles (21-26) of the locust extensor tibiae muscle, which are GABA-insensitive and have no inhibitory innervation. The actions of DHAVM on locust muscle appear to involve more than one site. Reversible actions of DHAVM appear to be related to GABA sensitivity and may involve the GABA receptor-ionophore complex. This is unlikely to be the site of action for the irreversible increases in C1- conductance caused by DHAVM.