Actions of Insecticidal Spinosyns on gamma-Aminobutyric Acid Responses from SmallDiameter Cockroach Neurons

The actions of spinosyns on insect gamma-aminobutyric acid (GABA) receptor function were assessed with small-diameter neurons from the central nervous system of the American cockroach (Periplaneta americana) by the whole-cell patch-clamp technique. In the absence of adenine nucleotides, neuronal responses to repeated applications of GABA diminished to zero within a matter of minutes. This effect is commonly referred to as rundown and, for these neurons, has previously been shown to be due to the absence of internal adenine nucleotides. Application of insecticidal spinosyns prior to the first application of GABA significantly accelerated the rundown of GABA responses, while noninsecticidal spinosyns had no effect on the rate of GABA response rundown. When GABA response rundown was blocked by the inclusion of adenosine 5ʹ triphosphate in the recording electrode, spinosyn A, the primary constituent of the novel insecticide spinosad, was found to elicit an irreversible current at concentrations above 1 nM. The electrical and pharmacological properties of this current suggest that it is carried by Cl- ions. Concurrent with the onset of this current, GABA responses were decreased and ultimately diminished to zero. In summary, insecticidal spinosyns have potent effects on the function of the GABA receptors of smalldiameter cockroach neurons and can elicit a small-amplitude Cl- current. These findings may have implications toward the insecticidal mechanism of action of spinosyns