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Visualization, Properties, and Functions of GABAergic Hippocampal Neurons Containing Calcium-Permeable Kainate and AMPA Receptors

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

Calcium-permeable kainate (CP-KARs) and AMPA (CP-AMPARs) receptors of the brain neurons are active participants of synaptic plasticity and neurotransmitter release trigger. In this paper, CP-KARs and CP-AMPARs were identified in hippocampal neuroglial culture on 14–17 day of cultivation by a characteristic Ca2+ response to a selective agonist of CP-KARs and CP-AMPARs, domoic acid (DA), and to a selective agonist of CP-KARs, ATPA. It was shown that DA at a concentration of 300 nM caused a rapid intracellular Ca2+ concentration increase in two minor subpopulations of neurons. Both subpopulations were found to be GABAergic neurons that were positively stained with antibodies against glutamate decarboxylase 65 and 67 (GAD65/67). The antagonist of CP-AMPARs, NASPM, did not suppress Ca2+ response to DA in the neurons of the first subpopulation. The selective agonist of CP-KARs, ATPA, increased [Ca2+]i to the same extent as DA only in the first subpopulation of GABAergic neurons. An inhibitor of GABA(A) receptors, bicuculline, did not increase the amplitude of Ca2+ response to DA in this subpopulation, indicating the absence of CP-KARs in the postsynaptic membrane, where GABA(A) receptors are located. Thus, these GABAergic neurons can be attributed to neurons containing CP-KARs, which are apparently located in the presynaptic membrane of the GABAergic neurons. The [Ca2+]i increase caused by the DA application in the second subpopulation was completely suppressed by NASPM, an inhibitor of CP-AMPARs. NASPM reduced the Ca2+ oscillations amplitude in the same subset, indicating the involvement of CP-AMPARs in the Ca2+ impulse formation during synchronous calcium activity. For this reason, the neurons of this subpopulation can be attributed to the GABAergic neurons containing CP-AMPARs. Most of the neurons in the hippocampal cell culture (70–85%) were not stained with antibodies against GAD65/67 and responded to the DA by increasing the calcium oscillations frequency with a delay. The amplitude of DA-induced oscillations increased in the presence of NASPM in the subpopulation of inhibitory neurons containing CP-KARs, indicating their innervation by inhibitory neurons containing CP-AMRARs. This increase in the Ca2+ oscillation amplitude in the inhibitory neurons containing CP-KARs correlated with a decrease in the amplitude of synchronous calcium activity in a large subpopulation (42 ± 6% of cells) of glutamatergic neurons, suggesting innervation of the latter by inhibitory neurons containing CP-KARs. Thus, GABAergic neurons containing CP-KARs and CP-AMPARs can work in tandem, controlling the activity of individual subpopulations of neurons.

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ACKNOWLEDGMENTS

The work was supported by the Committee of Science of the Ministry of Education of the Republic of Kazakhstan (project no. AP05133528).

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Authors and Affiliations

  1. Institute of Cell Biophysics, Russian Academy of Sciences, 142290, Pushchino, Moscow oblast, Russia

    V. P. Zinchenko, S. G. Gaidin, I. Yu. Teplov, A. M. Kosenkov, A. I. Sergeev & L. P. Dolgacheva

  2. Al-Farabi Kazakh national University, 050040, Almaty, Kazakhstan

    S. T. Tuleuhanov

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  1. V. P. Zinchenko
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Correspondence to V. P. Zinchenko.

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All procedures were performed in accordance with the European Communities Council Directive (November 24, 1986; 86/609/EEC) and the Declaration on humane treatment of animals. The protocol of experiments was approved by the Bioethics Committee of the Institute of Cell Biophysics, Russian Academy of Sciences.

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Translated by E. Puchkov

Abbreviations: AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid; CP-AMPARs, Ca2+-permeable AMPA receptors; NASPM, (1-naphthyl)acetyl spermine, a selective antagonist of CP-AMPARs; DA, domoic acid; CP-KARs, Ca2+-permeable kainate receptors; ATPA, (RS)-2-amino-3-(3-hydroxy-5-tret-butylisoxazole-4-yl)propanoic acid, a selective agonist of GluK1-containing kainate receptors; CGP-35348, (3-aminopropyl(diethoxymethyl)phosphic acid), an inhibitor of GABA(B) receptors; SCO, synchronous calcium oscillations.

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Zinchenko, V.P., Gaidin, S.G., Teplov, I.Y. et al. Visualization, Properties, and Functions of GABAergic Hippocampal Neurons Containing Calcium-Permeable Kainate and AMPA Receptors. Biochem. Moscow Suppl. Ser. A 14, 44–53 (2020). https://doi.org/10.1134/S1990747820010109

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