Degree

Doctor of Philosophy (PhD)

Department

Entomology

Document Type

Dissertation

Abstract

To identify novel insecticide target sites that can address the evolution of insecticide resistance, our group has tested the insecticidal potential of two potassium flux pathways: potassium-chloride (K+/Cl−) cotransporter (KCC) and inward rectifier potassium (Kir) channels. GABAergic signaling is the cornerstone of fast synaptic inhibition for neural signaling in arthropods; thus, the γ-aminobutyric acid (GABA)-receptor-chloride-channel (GRCC) complex has been a longstanding target for insecticides. Despite the importance to neuronal homeostasis, the upstream mechanisms enabling GRCC function are poorly defined. The data presented in this dissertation provide strong support that KCC is an essential ion transport system for proper neural function and functionally couples to GRCC by driving efflux of chloride ions. These data advance our knowledge of insect neural function and implicate KCC as a novel insecticide target. Inward rectifier potassium (Kir) channels are of growing interest within the field of insecticide science as they have been shown to be critical for proper function of various insect systems. Despite the increased focus to insect Kir channels, the physiological role and toxicological potential of neural Kir channels are poorly understood and thus, we combined chemical and genetic technologies to determine the physiological role and toxicological potential of insect neural Kir channels. Our data indicate Kir channels are critical for glial cell function, regulate neurotransmission through maintaining K+ ion homeostasis, and interact with KCC to help in shaping inhibitory neurotransmission through ligand-gated chloride channels. Taken together, the data presented in this dissertation begin to address knowledge deficits regarding mechanisms facilitating K+ homeostasis in insect neural systems and our incomplete understanding of function and toxicological potential of insect glial cells. These data can be used to guide development of novel therapeutics targeting neural function in humans.

Date

11-7-2022

Committee Chair

Swale, Daniel

Available for download on Friday, November 07, 2025

Included in

Entomology Commons

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