8.B.30. The Diguetoxin (Diguetoxin) Family
Insecticidal toxins frequently target voltage-gated cation channels (TC# 1.A.1) (Krapcho et al. 1995, Bloomquist et al. 1996). One such toxin, Dc1a, promotes opening of insect Nav channels. The toxin binds to the S1-S2 and S3-S4 loops in the domain II voltage-sensor (i.e., receptor site 4). The American cockroach P.americana is largely resistant to the effects of this toxin due to an unusual sequence within the domain II S1-S2 loop. In vivo, the toxin paralyzes lepidopteran and dipteran larvae. Paralyzed insects ultimately die from secondary effects of starvation and dehydration (Bende et al. 2014). The toxin has no effect on the human Nav channel subtypes Nav1.1 - Nav1.7, and has no effect on hERG (Kv11.1) and Kv2.1. It is non-toxic to mice (Bende et al. 2014).