The Effects Of Haedoxan A On Drosophila DmNa_v22 And Cockroach BgNa_v1-1a Sodium Channels

Haedoxan A(HA) is a lignan compound of 3,7-dioxabicyclo[3,3,0] octane isolated and identifited from the herbaceous perennial plant lopseed(Phryma leptostachya L.), which has higher insecticidal activity. The poisoning symptoms of treated insects were early cessation of feeding, muscle relaxation and, ultimately, death. It has been reported that HA acted on both axonal conduction and synaptic transmission, which not only delayed the decay rate of evoked excitatory junctional potentials(EJPs) and increased the frequency of miniature EJPs(mEJPs) on the Drosophila neuromuscular junction, but also caused a significant hyperpolarizing shift of the curve of insect sodium channels fast inactivation. Further investigation on sodium channel inactivation will be needed. In the present study, we established the gene expression system of Drosophila sodium channel DmNav22 and cockroach sodium channel BgNav1-1a in Xenopus laevis oocytes. Then we investigated the effects of HA on the voltage dependence of fast inactivation and slow inactivation of Drosophila DmNav22 and cockroach BgNav1-1a sodium channels. The main results are as follows:1. Drosophila DmNav22 and cockroach BgNav1-1a sodium channels were expressed in X. laevis oocytes, and the gating properties of these channels were examined with two electrode-voltage clamp.2. Effects of HA on the voltage dependence of fast and slow inactivation of insect sodium channels were tested. These results indicated that both 0.3 and 3 μmol/L HA could cause a hyperpolarizing shift of the voltage dependence of fast and slow inactivation of Drosophila DmNav22, and cockroach BgNav1-1a sodium channels expressed in X. laevis oocytes. It had a positive correlation between the shift and the concentration of haedoxane A.According to these results, we further speculated that HA acts on the insect voltage-gated sodium channels, and the insecticidal activity of it by affecting the fast and slow inactivation-gating properties in insect sodium channels.