Xenopus Oocytes: A Tool to Decipher Molecular Specificity of Insecticides towards Mammalian and Insect GABA—A Receptors

Abstract

The number of insect GABA receptors (GABAr) available for expression studies has been recently increased by the cloning of the Acyrthosiphon pisum (pea aphid) RDL subunits. This large number of cloned RDL subunits from pest and beneficial insects opens the door to parallel pharmacological studies on the sensitivity of these different insect GABAr to various agonists or antagonists. The resulting analysis of the molecular basis of the species-specific GABAr responses to insecticides is necessary not only to depict and understand species toxicity, but also to help at the early identification of unacceptable toxicity of insecticides toward beneficial insects such as Apis mellifera (honeybees). Using heterologous expression in Xenopus laevis oocytes, and two-electrode voltage-clamp recording to assess the properties of the GABAr, we performed a comparative analysis of the pharmacological sensitivity of RDL subunits from A. pisum, A. mellifera and Varroa destructor GABAr to three pesticides (fipronil, picrotoxin and dieldrin). These data were compared to similar characterizations performed on two Homo sapiens GABA-A receptors (α2β2γ2 and α2β2γ2). Our results underline a global conservation of the pharmacological profiles of these receptors, with some interesting species specificities, nonetheless, and suggest that this approach can be useful for the early identification of poorly specific molecules.

From squid giant axon to automated patch-clamp: electrophysiology in venom and antivenom research

“…In this technique, two intracellular electrodes (one voltage sensor and one current injector) are used to set the cell membrane potential to a desired value and to record the current across the membrane. By applying this method to oocytes from the African clawed frog, Xenopus laevis , various toxins that act on a wide range of ion channels, from the Na V and K V channels to ligand-gated nicotinic acetylcholine (nACh) and gamma aminobutyric acid (GABA) receptors ( Collins et al, 2009 ; Kvist et al, 2011 ; Bertaud et al, 2022 ), have been studied. The results of these studies provided valuable insights into how some toxins affect ion channel conductance, activation/inactivation dynamics, and opening/closing thresholds.…”

Bibliometric Analysis on GABA-A Receptors Research Based on CiteSpace and VOSviewer

“…18 Even some of the World's major insecticides. [19][20][21] As research in the GABAARs continues to expand, the literature also continues to progress. Despite this, the topics and characteristics of publications on the GABA-A receptor channels have not been investigated.…”

The Xenopus Oocyte: A Tool for Membrane Biology

“…The expression of various receptors and ion channels therefore constitutes most of the papers published in this Special Issue. Using a classical electrophysiology approach based on two-electrode voltage clamp recording, Bertaud et al [1] compared the effect of several widely used insecticides on human and insect GABA receptors. The use of the Xenopus oocyte is underlined by the pharmacological differences that exist between these GABA receptors in their differential sensitivity to insecticides.…”