Functional interactions between potassium-chloride cotransporter (KCC) and inward rectifier potassium (Kir) channels in the insect central nervous system

Functional interactions between potassium-chloride cotransporter (KCC) and inward rectifier potassium (Kir) channels in the insect central nervous system

The K+/Cl− cotransporter (KCC) is the primary mechanism by which mature neurons maintain low intracellular chloride (Cl−) concentration and has been shown to be functionally coupled to the GABA-gated chloride channels (GGCC) in Drosophila central neurons. Further, pharmacological inhibition of KCC h...

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Bibliographic Details
Published in:Pesticide biochemistry and physiology 2023-05, Vol.192, p.105389-105389, Article 105389
Main Authors: Chen, Rui, Swale, Daniel R.
Format: Article
Language:eng
Subjects:
Aedes aegypti
Animals
Central Nervous System - metabolism
Chlorides - metabolism
Chlorides - pharmacology
Drosophila - metabolism
GABA
gamma-Aminobutyric Acid - metabolism
Inhibitory neurotransmission
Insecticide
Potassium - metabolism
Potassium Chloride - metabolism
Symporters - metabolism
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Summary:The K+/Cl− cotransporter (KCC) is the primary mechanism by which mature neurons maintain low intracellular chloride (Cl−) concentration and has been shown to be functionally coupled to the GABA-gated chloride channels (GGCC) in Drosophila central neurons. Further, pharmacological inhibition of KCC has been shown to lead to acute toxicity of mosquitoes that highlights the toxicological relevance of insect KCC. Yet, gaps in knowledge remain regarding physiological drivers of KCC function and interactions of ion flux mechanisms upstream of GGCC in insects. Considering this, we employed electrophysiological and fluorescent microscopy techniques to further characterize KCC in the insect nervous system. Fluorescent microscopy indicated insect KCC2 is expressed in rdl neurons, which is the neuron type responsible for GABA-mediated neurotransmission, and are coexpressed with inward rectifier potassium (Kir) 2 channels. Coexpression of Kir2 and KCC2 suggested the possibility of functional coupling between these two K+ flux pathways. Indeed, extracellular recordings of Drosophila CNS showed pre-block of Kir channels prior to block of KCC led to a significant (P 
ISSN:0048-3575
1095-9939