Insertion of Calcium-Permeable AMPA Receptors during Epileptiform Activity In Vitro Modulates Excitability of Principal Neurons in the Rat Entorhinal Cortex

Epileptic activity leads to rapid insertion of calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (CP-AMPARs) into the synapses of cortical and hippocampal glutamatergic neurons, which generally do not express them. The physiological significance of this process is not...

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Autores principales:	Dmitry V. Amakhin, Elena B. Soboleva, Anton V. Chizhov, Aleksey V. Zaitsev
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	epilepsy synaptic plasticity NMDA receptor excitatory postsynaptic current IEM-1460 patch-clamp Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/0d194f09872a4b5eac088d1671ef5fee
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spelling	oai:doaj.org-article:0d194f09872a4b5eac088d1671ef5fee2021-11-25T17:53:58ZInsertion of Calcium-Permeable AMPA Receptors during Epileptiform Activity In Vitro Modulates Excitability of Principal Neurons in the Rat Entorhinal Cortex10.3390/ijms2222121741422-00671661-6596https://doaj.org/article/0d194f09872a4b5eac088d1671ef5fee2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12174https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Epileptic activity leads to rapid insertion of calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (CP-AMPARs) into the synapses of cortical and hippocampal glutamatergic neurons, which generally do not express them. The physiological significance of this process is not yet fully understood; however, it is usually assumed to be a pathological process that augments epileptic activity. Using whole-cell patch-clamp recordings in rat entorhinal cortex slices, we demonstrate that the timing of epileptiform discharges, induced by 4-aminopyridine and gabazine, is determined by the shunting effect of Ca<sup>2+</sup>-dependent slow conductance, mediated predominantly by K<sup>+</sup>-channels. The blockade of CP-AMPARs by IEM-1460 eliminates this extra conductance and consequently increases the rate of discharge generation. The blockade of NMDARs reduced the additional conductance to a lesser extent than the blockade of CP-AMPARs, indicating that CP-AMPARs are a more significant source of intracellular Ca<sup>2+</sup>. The study’s main findings were implemented in a mathematical model, which reproduces the shunting effect of activity-dependent conductance on the generation of discharges. The obtained results suggest that the expression of CP-AMPARs in principal neurons reduces the discharge generation rate and may be considered as a protective mechanism.Dmitry V. AmakhinElena B. SobolevaAnton V. ChizhovAleksey V. ZaitsevMDPI AGarticleepilepsysynaptic plasticityNMDA receptorexcitatory postsynaptic currentIEM-1460patch-clampBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12174, p 12174 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	epilepsy synaptic plasticity NMDA receptor excitatory postsynaptic current IEM-1460 patch-clamp Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	epilepsy synaptic plasticity NMDA receptor excitatory postsynaptic current IEM-1460 patch-clamp Biology (General) QH301-705.5 Chemistry QD1-999 Dmitry V. Amakhin Elena B. Soboleva Anton V. Chizhov Aleksey V. Zaitsev Insertion of Calcium-Permeable AMPA Receptors during Epileptiform Activity In Vitro Modulates Excitability of Principal Neurons in the Rat Entorhinal Cortex
description	Epileptic activity leads to rapid insertion of calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (CP-AMPARs) into the synapses of cortical and hippocampal glutamatergic neurons, which generally do not express them. The physiological significance of this process is not yet fully understood; however, it is usually assumed to be a pathological process that augments epileptic activity. Using whole-cell patch-clamp recordings in rat entorhinal cortex slices, we demonstrate that the timing of epileptiform discharges, induced by 4-aminopyridine and gabazine, is determined by the shunting effect of Ca<sup>2+</sup>-dependent slow conductance, mediated predominantly by K<sup>+</sup>-channels. The blockade of CP-AMPARs by IEM-1460 eliminates this extra conductance and consequently increases the rate of discharge generation. The blockade of NMDARs reduced the additional conductance to a lesser extent than the blockade of CP-AMPARs, indicating that CP-AMPARs are a more significant source of intracellular Ca<sup>2+</sup>. The study’s main findings were implemented in a mathematical model, which reproduces the shunting effect of activity-dependent conductance on the generation of discharges. The obtained results suggest that the expression of CP-AMPARs in principal neurons reduces the discharge generation rate and may be considered as a protective mechanism.
format	article
author	Dmitry V. Amakhin Elena B. Soboleva Anton V. Chizhov Aleksey V. Zaitsev
author_facet	Dmitry V. Amakhin Elena B. Soboleva Anton V. Chizhov Aleksey V. Zaitsev
author_sort	Dmitry V. Amakhin
title	Insertion of Calcium-Permeable AMPA Receptors during Epileptiform Activity In Vitro Modulates Excitability of Principal Neurons in the Rat Entorhinal Cortex
title_short	Insertion of Calcium-Permeable AMPA Receptors during Epileptiform Activity In Vitro Modulates Excitability of Principal Neurons in the Rat Entorhinal Cortex
title_full	Insertion of Calcium-Permeable AMPA Receptors during Epileptiform Activity In Vitro Modulates Excitability of Principal Neurons in the Rat Entorhinal Cortex
title_fullStr	Insertion of Calcium-Permeable AMPA Receptors during Epileptiform Activity In Vitro Modulates Excitability of Principal Neurons in the Rat Entorhinal Cortex
title_full_unstemmed	Insertion of Calcium-Permeable AMPA Receptors during Epileptiform Activity In Vitro Modulates Excitability of Principal Neurons in the Rat Entorhinal Cortex
title_sort	insertion of calcium-permeable ampa receptors during epileptiform activity in vitro modulates excitability of principal neurons in the rat entorhinal cortex
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0d194f09872a4b5eac088d1671ef5fee
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Insertion of Calcium-Permeable AMPA Receptors during Epileptiform Activity In Vitro Modulates Excitability of Principal Neurons in the Rat Entorhinal Cortex

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