Inwardly Rectifying Potassium (Kir) Channels Represent a Critical Ion Conductance Pathway in the Nervous Systems of Insects

Rui Chen,Daniel R Swale

doi:10.1038/s41598-018-20005-z

Abstract

A complete understanding of the physiological pathways critical for proper function of the insect nervous system is still lacking. The recent development of potent and selective small-molecule modulators of insect inward rectifier potassium (Kir) channels has enabled the interrogation of the physiological role and toxicological potential of Kir channels within various insect tissue systems. Therefore, we aimed to highlight the physiological and functional role of neural Kir channels the central nervous system, muscular system, and neuromuscular system through pharmacological and genetic manipulations. Our data provide significant evidence that Drosophila neural systems rely on the inward conductance of K+ ions for proper function since pharmacological inhibition and genetic ablation of neural Kir channels yielded dramatic alterations of the CNS spike discharge frequency and broadening and reduced amplitude of the evoked EPSP at the neuromuscular junction. Based on these data, we conclude that neural Kir channels in insects (1) are critical for proper function of the insect nervous system, (2) represents an unexplored physiological pathway that is likely to shape the understanding of neuronal signaling, maintenance of membrane potentials, and maintenance of the ionic balance of insects, and (3) are capable of inducing acute toxicity to insects through neurological poisoning.

Highlights

Recent genetic and pharmacological evidence suggests that Kir channels could represent viable targets for new insecticides
It is possible that the mortality is due to complete systems failure stemming from ubiquitous expression of Kir channels or due to accumulated waste that remains due to impaired Malpighian tubule function[3], it is reasonable to predict that VU041 is directly altering the functional capacity of Kir channels expressed in the nervous system to yield toxicity
Considering (1) the foundational role of Kir channels in mammalian and insect cellular physiology, (2) deletion of irk[2] gene in Drosophila is homozygous lethal[22], (3) the signs of intoxication after exposure to Kir channel modulators being reminiscent of neurological poisoning, and (4) the overexpression of Kir mRNA in mosquito and Drosophila neural tissues, we hypothesized that Kir channels regulate neuronal signaling and excitability of insect nervous systems and are a critical conductance pathway for proper functioning of the insect nervous system

Summary

Introduction

Recent genetic and pharmacological evidence suggests that Kir channels could represent viable targets for new insecticides. Electrophysiological recordings from an excised CNS of D. melanogaster is possible[20] and further, the gene encoding Kir[2], termed irk[2], is highly concentrated in the adult head, CNS, and the thoracic-abdominal ganglia[21] This suggests that D. melanogaster may represent a suitable substitute for mosquitoes and will enable the characterization of the physiological role Kir channels have in the insect nervous system. Considering (1) the foundational role of Kir channels in mammalian and insect cellular physiology, (2) deletion of irk[2] gene in Drosophila is homozygous lethal[22], (3) the signs of intoxication after exposure to Kir channel modulators being reminiscent of neurological poisoning, and (4) the overexpression of Kir mRNA in mosquito and Drosophila neural tissues, we hypothesized that Kir channels regulate neuronal signaling and excitability of insect nervous systems and are a critical conductance pathway for proper functioning of the insect nervous system. Data collected in this study begin to bridge the fundamental knowledge gap regarding unexplored physiological pathways in the insect nervous system that will provide a more holistic understanding to neuronal excitability and neurotransmission of insects

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