Although greater than 90% of insecticides target the nervous system, a complete understanding of the physiological pathways critical for proper function of the insect nervous system is still lacking. In mammals, inward rectifier potassium (Kir) channels are known to maintain the resting membrane potential and regulate the firing threshold in neuronal cells, yet their role in the insect nervous system remains unexplored. Therefore, this work aimed to characterize the role of Kir channels in the insect nervous system and determine the potential for the development of insecticides targeting neuronal Kir channels. Exposure of Aedes aegypti and Drosophila melanogaster to VU041, an insect specific inhibitor of Kir channels, induced acute toxicity reminiscent of nervous system poisoning. We performed neurophysiological recordings of the excised Drosophila central nervous system (CNS) to test the hypothesis that Kir channels are critical for proper neural transmission in insects. Exposure to 300 nM VU041 increased the spike discharge frequency by 32 ± 6%, a statistically significant increase when compared to baseline spike discharge frequency (P&lt;0.05). At increasing concentrations, VU041 was found to have a depressant effect on the Drosophila CNS activity with an IC50 of 23 μM. Immunohistochemical studies against the Drosophila CNS indicate that Kir channels are localized to the neural lamella, which is the extracellular matrix layer of the blood brain barrier and is important for maintaining the K+ ion gradient of the CNS. Based on the data collected in this study, we hypothesize that the function of Kir channels in the insect nervous system is to regulate extracellular potassium concentrations [K+]o during neural activity by distributing [K+]o ions to areas of low internal K+ concentrations, a process termed K+ spatial buffering. Electrophysiological data supporting this hypothesis and the potential for neural Kir channels to be a target for insecticides will be discussed.

Altering K+ spatial buffering events through modulation of inward rectifier potassium (Kir) channels leads to nervous system failure and insect mortality

256th National Meeting (2018)

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