The Role Of DSC1 Channel In The Sensory-Central Nervous System-Motor Circuit Of Four Strains Of Drosophila Larvae And The Effect Of Haedoxan A On It

In recent years,it has been found that the DSC1（Drosophila sodium channel 1）channel is a voltage-gated divalent cation channel only existing in invertebrates such as insects.It is generally believed that its function is mainly to regulate the stability of the neural circuit,especially under adverse conditions,it plays an important role in maintaining the excitability of the nervous system.Since the DSC1 channel exists only in invertebrates,it has attracted attention for research and development of insecticides targeting the DSC1 channel and being safe for mammals.Haedoxan A is major component with higher insecticidal activity in Phryma leptostachya,which was comparable with commercial synthetic pyrethroids.Previous research results showed that haedoxan A delayed the decay rate of excitatory junction potential（EJP）in neuromuscular junction of Drosophila melanogaster,increased the frequency of miniature excitatory junction potentials on Drosophila neuromuscular junction.In this paper,based on the four Drosophila strains-w¹¹¹⁸（wild type）、DSC1^-/-（DSC1knockout mututant）、para^ts1（pyrethroid-resistant mututant）and para^ts1;DSC1^-/-（double mutant）,we discussed the role of DSC1 channel in the sensory-CNS system-motor circuit by praxeology and electrophysiology.Besides,we compared the effects of haedoxan A to the sensory-CNS system-motor circuit of four Drosophila strains larvae.The main results are as follows:1.Behavioral observations on the four strains of Drosophila larvae showed that the Drosophila larvae knocked out of the DSC1 channel had no obvious behavioral defects compared with the Drosophila larvae that had not been knocked out of the DSC1 channel,but In the state of starvation,the Drosophila larvae that knocked out the DSC1 channel had a lower ability to explore the surrounding environment and food than the normal strain.The electrophysiological tests of the sensory-CNS system-motor circuit of four strains of Drosophila larvae showed that the larvae of the w¹¹¹⁸ and para^ts1 strains after starvation treatment had no significant difference in the EJP frequency of the neural circuit.The EJP frequency of the DSC1^-/-and para^ts1;DSC1^-/-neural circuit is lower than the normal state.It showed that the excitability of the sensory-CNS system-motor circuit of the two strains of Drosophila larvae that knocked out the DSC1 channel was reduced after starvation,which is consistent with the results of the tomato slice behavioral observation test.This suggests that the presence of the DSC1 channel plays an important role in maintaining and regulating the stability of the neural circuit under starvation stress conditions.2.After treatment of four Drosophila strain larvae with haedoxan A for 2h,the attenuation amplitude of EJP frequency of sensory-CNS system-motor circuit of four strains of Drosophila larvae was found to be DSC1^-/->para^ts1;DSC1^-/->w¹¹¹⁸>para^ts1.Further treatment of Drosophila larval sensory-CNS system-motor circuit in vitro specimens with haedoxan A for 20min,we found that the EJP frequency of the sensory-CNS system-motor circuit of the four strains of Drosophila larvae were obviously improved,the magnitude of the increase in the EJP frequency of the sensory-CNS system-motor circuit is para^ts1>w¹¹¹⁸>para^ts1;DSC1^-/->DSC1^-/-,it is consistent with the test results of the haedoxan A drip treatment of Drosophila larvae in vivo.This indicated that haedoxan A delays the attenuation of sensory-CNS system-motor circuit potential activity,and enhances the excitability of sensory-CNS system-motor circuit.Besides,it also showed that the pyrethroid Mutant strains which produce resistance to insecticides are more susceptible to haedoxan A,and the sensitivity of the Drosophila larvae knocking out the DSC1 channel to haedoxan A is reduced.The above findings further confirmed that in the stress response of insects,DSC1channel plays an important role in regulating the nervous circuit and neuronal excitation stability;mutant strains resistant to pyrethroid insecticides instead of haedoxan A is more sensitive.It is speculated that haedoxan A may have some negative cross-resistance with pyrethroid insecticides,and its action site may be related to the mutation site in the anti-promethrin strain;haedoxan A affects the DSC1 channel to maintain and regulate the excitatory activity of the neural circuit,delays the attenuation of the EJP frequency of the sensory-CNS system-motor circuit of the Drosophila larvae,and enhances the excitability of the sensory-CNS system-motor circuit.It is speculated that haedoxan A may act on the DSC1 channel.As for the specific site of action of haedoxan A and how the DSC1 channel interacts with it,further studies are needed.