A Model for Predicting Cation Selectivity and Permeability in AMPA and NMDA Receptors Based on Receptor Subunit Composition

Glutamatergic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartate) receptors are implicated in diverse functions ranging from synaptic plasticity to cell death. They are heterotetrameric proteins whose subunits are derived from multiple distinct gene families....

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Autores principales:	Sampath Kumar, Sanjay S. Kumar
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	ion selectivity ion permeability AMPA receptors NMDA receptors subunit composition charge permeability equation Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/dc9012e97f244e56bc70d02bb7fe1ec9
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spelling	oai:doaj.org-article:dc9012e97f244e56bc70d02bb7fe1ec92021-12-01T14:11:12ZA Model for Predicting Cation Selectivity and Permeability in AMPA and NMDA Receptors Based on Receptor Subunit Composition1663-356310.3389/fnsyn.2021.779759https://doaj.org/article/dc9012e97f244e56bc70d02bb7fe1ec92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnsyn.2021.779759/fullhttps://doaj.org/toc/1663-3563Glutamatergic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartate) receptors are implicated in diverse functions ranging from synaptic plasticity to cell death. They are heterotetrameric proteins whose subunits are derived from multiple distinct gene families. The subunit composition of these receptors determines their permeability to monovalent and/or divalent cations, but it is not entirely clear how this selectivity arises in native and recombinantly-expressed receptor populations. By analyzing the sequence of amino acids lining the selectivity filters within the pore forming membrane helices (M2) of these subunits and by correlating subunit stoichiometry of these receptors with their ability to permeate Na+ and/or Ca2+, we propose here a mathematical model for predicting cation selectivity and permeability in these receptors. The model proposed is based on principles of charge attractivity and charge neutralization within the pore forming region of these receptors; it accurately predicts and reconciles experimental data across various platforms including Ca2+ permeability of GluA2-lacking AMPARs and ion selectivity within GluN3-containing di- and tri-heteromeric NMDARs. Additionally, the model provides insights into biophysical mechanisms regulating cation selectivity and permeability of these receptors and the role of various subunits in these processes.Sampath KumarSanjay S. KumarFrontiers Media S.A.articleion selectivityion permeabilityAMPA receptorsNMDA receptorssubunit compositioncharge permeability equationNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Synaptic Neuroscience, Vol 13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ion selectivity ion permeability AMPA receptors NMDA receptors subunit composition charge permeability equation Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	ion selectivity ion permeability AMPA receptors NMDA receptors subunit composition charge permeability equation Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Sampath Kumar Sanjay S. Kumar A Model for Predicting Cation Selectivity and Permeability in AMPA and NMDA Receptors Based on Receptor Subunit Composition
description	Glutamatergic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartate) receptors are implicated in diverse functions ranging from synaptic plasticity to cell death. They are heterotetrameric proteins whose subunits are derived from multiple distinct gene families. The subunit composition of these receptors determines their permeability to monovalent and/or divalent cations, but it is not entirely clear how this selectivity arises in native and recombinantly-expressed receptor populations. By analyzing the sequence of amino acids lining the selectivity filters within the pore forming membrane helices (M2) of these subunits and by correlating subunit stoichiometry of these receptors with their ability to permeate Na+ and/or Ca2+, we propose here a mathematical model for predicting cation selectivity and permeability in these receptors. The model proposed is based on principles of charge attractivity and charge neutralization within the pore forming region of these receptors; it accurately predicts and reconciles experimental data across various platforms including Ca2+ permeability of GluA2-lacking AMPARs and ion selectivity within GluN3-containing di- and tri-heteromeric NMDARs. Additionally, the model provides insights into biophysical mechanisms regulating cation selectivity and permeability of these receptors and the role of various subunits in these processes.
format	article
author	Sampath Kumar Sanjay S. Kumar
author_facet	Sampath Kumar Sanjay S. Kumar
author_sort	Sampath Kumar
title	A Model for Predicting Cation Selectivity and Permeability in AMPA and NMDA Receptors Based on Receptor Subunit Composition
title_short	A Model for Predicting Cation Selectivity and Permeability in AMPA and NMDA Receptors Based on Receptor Subunit Composition
title_full	A Model for Predicting Cation Selectivity and Permeability in AMPA and NMDA Receptors Based on Receptor Subunit Composition
title_fullStr	A Model for Predicting Cation Selectivity and Permeability in AMPA and NMDA Receptors Based on Receptor Subunit Composition
title_full_unstemmed	A Model for Predicting Cation Selectivity and Permeability in AMPA and NMDA Receptors Based on Receptor Subunit Composition
title_sort	model for predicting cation selectivity and permeability in ampa and nmda receptors based on receptor subunit composition
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/dc9012e97f244e56bc70d02bb7fe1ec9
work_keys_str_mv	AT sampathkumar amodelforpredictingcationselectivityandpermeabilityinampaandnmdareceptorsbasedonreceptorsubunitcomposition AT sanjayskumar amodelforpredictingcationselectivityandpermeabilityinampaandnmdareceptorsbasedonreceptorsubunitcomposition AT sampathkumar modelforpredictingcationselectivityandpermeabilityinampaandnmdareceptorsbasedonreceptorsubunitcomposition AT sanjayskumar modelforpredictingcationselectivityandpermeabilityinampaandnmdareceptorsbasedonreceptorsubunitcomposition
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A Model for Predicting Cation Selectivity and Permeability in AMPA and NMDA Receptors Based on Receptor Subunit Composition

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