Postdoctoral researcher Rui Chen won best research poster in the EPI Research Day 2023 early-stage investigator poster competition. Her poster consisted of several interrelated projects, but her main research focused on characterizing the function of inwardly rectifying potassium (Kir) channels in insects nervous system.
“It’s just interesting to ask why this is happening,” said Chen. “Though the processes are struggling, the moment that we get close to our assumptions make me so happy.”
Her study aimed to determine if Kir channels expressed in glia cells contribute to nerve firing and how Kir inhibition negatively impacts neuronal function. Chen found that Kir channels in glia cells assist the potassium movement in neuronal functions. As a result, insecticides could potentially target insect glial cells.
Chen received her Bachelor of Agronomy at the Northwest Agriculture and Forestry University in China. Her interest in studying biomedical targets for insecticides began in graduate school at Louisiana State University, where she earned a Ph.D. in Entomology. After she earned her degree, she moved to Florida to continue her research on kir channels and KCC with her advisor Dr. Daniel Swale.
“When I won, I was kind of surprised at the beginning,” Chen said. “But, later, I felt happy.”
Chen is considering using her award to attend a scientific conference in October. With a recent PhD, she deliberates whether she wants to pursue a career in the industry or in academia. Nevertheless, she leans more toward the latter and sees a potential future in achieving funding to continue her research.
Employing chemical genetics to develop insect glia as a cellular target for insecticides
Collaborators
- Rui Chen – Department of Entomology and Nematology, Emerging Pathogens Institute, College of Agricultural and Life Sciences, University of Florida
- Daniel Swale – Department of Entomology and Nematology, Emerging Pathogens Institute, College of Agricultural and Life Sciences, University of Florida
Introduction
The development of novel insecticide targets has been of consistent interest to the field of insecticide science, yet few new biochemical targets have emerged over the past two decades. Insect neurons are the target tissue for >85% of commercialized insecticides, thus it is surprising the functional roles of insect glial cells remain poorly understood and there are no glia-directed insecticides. Recent work has shown expression of various ion channels in insect glia cells, raising the intriguing possibility that glial cells contribute to neuronal function of insects and may represent a cellular target for insecticide design. Considering this, we tested the hypothesis that inwardly rectifying potassium (Kir) channels expressed in glia cells contribute to nerve firing and Kir inhibition will have deleterious consequences to neuronal function.
Methods and results
To test this hypothesis, we built Kir2 promoter drive GAL4 fly line, combined with UAS and LexA/LexAop binary system, we showed Kir2 channel subunits are primarily expressed in perineural, subperineural, and astrocyte-like glia in the Drosophila melangoster CNS. Patch clamp studies confirmed membrane expression in spg and astrocyte-like glia with an average of 131.9 ± 72.9 pA and 182.3 ± 40.9 pA of barium inhibitable current, respectively. These data led us to speculate Kir channels constitute a mechanism for rapid clearance of K+ ions from the extracellular space during neuronal activity and thus, inhibition of glial Kir channels would result in membrane depolarization and increased firing. Therefore, we performed extracellular recordings of Drosophila descending neurons and found pharmacological inhibition of Kir channels significantly (P<0.05) increased the firing rate and lead to nerve death (IC50: 23 µM). Importantly, inhibition of glial cell function with Kir specific pharmacophores resulted in acute lethality that highlights the potential for developing novel mode- and mechanism- insecticides targeting glial cell function.
Conclusions
Kirs express in glia cells and are responsible for the potassium movement in neuronal functions. Further, insect glial Kirs could be potentially insecticide target site.