DSC1-dependent modulation of synaptic activities by haedoxan A in Drosophila melanogaster

Authors: XIE, XINGTAO - Northwest A&f University; REN, YAXIN - Northwest A&f University; CHEN, XUETING - Northwest A&f University; Du, Yuzhe - Cathy; DONG, KE - Duke University; HU, ZHAONONG - Northwest A&f University

Submitted to: Journal of Insect Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/19/2023
Publication Date: 2/8/2023
Citation: Xie, X., Ren, Y., Chen, X., Du, Y., Dong, K., Hu, Z. 2023. DSC1-dependent modulation of synaptic activities by haedoxan A in Drosophila melanogaster. Journal of Insect Science. https://doi.org/10.1111/1744-7917.13180.
DOI: https://doi.org/10.1111/1744-7917.13180

Interpretive Summary: Fruit fly sodium channel 1 (DSC1) is a cation channel that mediates neuronal excitability in insects. Prior research revealed that adults and larvae from DSC1 knockout fruit fly conferred different susceptibility to pyrethroids, indicating the vital regulation role of DSC1 in the nervous system. Haedoxan A (HA) is an insecticidal compound isolated from the medical plant Phryma leptostachya. Herein, we performed the bioassay and electrophysiological approach to test the biological and neural changes in the larval fruit fly with/without DSC1 knockout with HA treatment. Four different fruit flies were used in the tests from , w1118 (a sensitive strain), DSC1-/- (a DSC1 knockout mutant strain), parats1 (carrying a pyrethroid-resistant mutation in sodium channel) and parats1; DSC1-/- (a double mutant strain). Bioassay results showed that knockout DSC1 increased the resistance to HA in both sensitive (w1118) and pyrethroid-resistant (parats1) fruit fly larvae. Electrophysiology results indicated that DSC1 not only regulated the insecticidal activity of HA, but also maintained the stability of neural circuits through functional interaction with voltage-gated sodium channels (VGSCs). Our study provided useful information for elucidating the regulating of DSC1 in involving the action of HA in the insect nerve system.

Technical Abstract: Drosophila sodium channel 1 (DSC1) encodes a voltage-gated divalent cation channel that mediates neuronal excitability in insects, which later proved to be more permeable to Ca2+. Prior research revealed that adults and larvae from DSC1 knockout Drosophila melanogaster strain conferred different susceptibility to pyrethroids, indicating the vital regulation role of DSC1 in the nervous system. Haedoxan A (HA) is an insecticidal lignan compound isolated from the medical plant Phryma leptostachya. Herein, we performed the bioassay and electrophysiological approach to test the biological and neural changes in the larval Drosophila with/without DSC1 knockout with HA treatment. The larvae used in the tests were from four different strains, w1118 (a sensitive strain), DSC1-/- (a DSC1 knockout mutant strain), parats1 (carrying a pyrethroid-resistant mutation in sodium channel) and parats1; DSC1-/- (a double mutant strain). Bioassay results showed that knockout DSC1 increased the resistance to HA in both sensitive (w1118) and pyrethroid-resistant (parats1) Drosophila larvae. Electrophysiology results implicated that HA delayed the decay rate and increased the frequency of miniature excitatory junctional potentials (mEJPs) of three strains of Drosophila larvae except for parats1; DSC1-/- strain. These results indicated that DSC1 not only regulated the insecticidal activity of HA, but also maintained the stability of neural circuits through functional interaction with voltage-gated sodium channels (VGSCs). Moreover, the neuromuscular synapse excitatory activities of parats1; DSC1-/- larvae were more sensitive to HA than DSC1-/- larvae, which further confirmed the functional contribution of DSC1 to neuronal excitability. Hence, our study provided useful information for elucidating the regulatory mechanisms of DSC1 in involving the action of HA in the insect nerve system.