The nervous system is the target of nearly 90% of all deployed insecticides, yet insecticide resistance is severely reducing the effectiveness of the currently approved chemical classes. To combat the growing levels of insecticide resistance, our group is exploring inward rectifying potassium (Kir) channels as viable target sites for insecticide development.  Although the functions of Kir channels in insects are significantly less understood when compared to mammals, it has been shown that they play important physiological roles in osmoregulation, immunity, development, and ion transport in insect Malpighian tubules. In the classical sense, Kir channels are known to maintain the resting membrane potential and regulate the firing threshold in mammalian neuronal cells, yet their role in the insect nervous system is currently 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.  The small molecule inhibitor, termed VU001, was shown to induce lethargic tendencies, acute toxicity and a flightless phenotype to Aedes aegypti and Drosophila melanogaster, which is likely due impairment of nervous system. Neurophysiological recordings of the Drosophila central nervous system (CNS) showed that VU001 induces hyperexcitation followed by depression of the CNS spike discharge frequency, suggesting potential roles in maintenance of axonal properties. Also, exposure to VU001 on the neuromuscular junction of Drosophila causes an altered excitatory postsynaptic potential waveform at 10 uM and a complete cessation of the evoked action potential at 30 μM VU001. Studies to explore the cellular and sub-cellular expression patterns, roles in K+ spatial buffering, and discovery of novel small-molecule scaffolds will be presented. <br/>

Physiological characterization of inward rectifying potassium (Kir) channels in the insect nervous systems

254th National Meeting (2017)

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