Glutamate Receptor-Cation Channel Complex: An Unexploited Target for Mosquito Control

2017 ◽  
pp. 111-124 ◽  
Author(s):  
Aaron D. Gross ◽  
Rafique Islam ◽  
Jeffrey R. Bloomquist
Keyword(s):  
Glutamate Receptor ◽  
Mosquito Control ◽  
Cation Channel

scholarly journals Activation of the TRPC1 cation channel by metabotropic glutamate receptor mGluR1

Nature ◽  
2003 ◽  
Vol 426 (6964) ◽  
pp. 285-291 ◽  
Author(s):  
Sang Jeong Kim ◽  
Yu Shin Kim ◽  
Joseph P. Yuan ◽  
Ronald S. Petralia ◽  
Paul F. Worley ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Cation Channel ◽  
Metabotropic Glutamate

scholarly journals Nonselective cation permeation in an AMPA-type glutamate receptor

2021 ◽  
Vol 118 (8) ◽  
pp. e2012843118
Author(s):  
Johann Biedermann ◽  
Sebastian Braunbeck ◽  
Andrew J. R. Plested ◽  
Han Sun
Keyword(s):  
Glutamate Receptor ◽  
Ampa Receptors ◽  
Binding Sites ◽  
Alkali Metals ◽  
Molecular Mechanisms ◽  
Md Simulations ◽  
Cation Channel ◽  
Ion Binding ◽  
Anion Permeation ◽  
Ion Binding Sites

Fast excitatory synaptic transmission in the central nervous system relies on the AMPA-type glutamate receptor (AMPAR). This receptor incorporates a nonselective cation channel, which is opened by the binding of glutamate. Although the open pore structure has recently became available from cryo-electron microscopy (Cryo-EM), the molecular mechanisms governing cation permeability in AMPA receptors are not understood. Here, we combined microsecond molecular dynamic (MD) simulations on a putative open-state structure of GluA2 with electrophysiology on cloned channels to elucidate ion permeation mechanisms. Na+, K+, and Cs+ permeated at physiological rates, consistent with a structure that represents a true open state. A single major ion binding site for Na+ and K+ in the pore represents the simplest selectivity filter (SF) structure for any tetrameric cation channel of known structure. The minimal SF comprised only Q586 and Q587, and other residues on the cytoplasmic side formed a water-filled cavity with a cone shape that lacked major interactions with ions. We observed that Cl− readily enters the upper pore, explaining anion permeation in the RNA-edited (Q586R) form of GluA2. A permissive architecture of the SF accommodated different alkali metals in distinct solvation states to allow rapid, nonselective cation permeation and copermeation by water. Simulations suggested Cs+ uses two equally populated ion binding sites in the filter, and we confirmed with electrophysiology of GluA2 that Cs+ is slightly more permeant than Na+, consistent with serial binding sites preferentially driving selectivity.

scholarly journals Non-selective cation permeation in an AMPA-type glutamate receptor

2020 ◽  
Author(s):  
Johann Biedermann ◽  
Sebastian Braunbeck ◽  
Andrew J. R. Plested ◽  
Han Sun
Keyword(s):  
Molecular Dynamics ◽  
Ion Channel ◽  
Binding Site ◽  
Glutamate Receptor ◽  
Binding Sites ◽  
Alkali Metals ◽  
Molecular Mechanisms ◽  
Cation Channel ◽  
Ion Binding ◽  
Major Ion

AbstractFast excitatory synaptic transmission in the central nervous system relies on the AMPA-type glutamate receptor (AMPAR). This receptor incorporates a non-selective cation channel which is opened by the binding of glutamate. Although the open pore structure has recently became available from cryo-electron microscopy (Cryo-EM), the molecular mechanisms governing cation permeability in AMPA receptors are not understood. Here, we combined microsecond molecular dynamics (MD) simulations on a putative open state structure of GluA2 with electrophysiology on cloned channels to elucidate ion permeation mechanisms. Na+, K+ and Cs+ permeated at physiological rates, consistent with a structure that represents a true open state. A single major ion binding site for Na+ and K+ in the pore represents the simplest selectivity filter (SF) structure for any tetrameric cation channel of known structure. The minimal SF comprised only Q586 and Q587, and other residues on the cytoplasmic side formed a cone- shaped void that lacked major interactions with ions. We observed Cl- invasion of the upper pore, explaining anion permeation in the edited form of GluA2. A permissive architecture of the SF accommodated different alkali metals in distinct solvation states to allow rapid, non-selective cation permeation, and co-permeation by water. Simulations suggested Cs+ uses two equally populated ion binding sites in the filter and we confirmed with electrophysiology of GluA2 that Cs+ is more permeant than Na+, consistent with serial binding sites preferentially driving selectivity.Significance StatementAMPA-type glutamate receptors (AMPARs) are key actors in neurotransmission, making the final step in a relay of excitability from one brain cell to another. The receptor contains an integral ion channel, which, when opened by neurotransmitter binding, permits sodium and other cations to cross the cell membrane. We investigated permeation of sodium, potassium and caesium in an AMPAR at the atomistic level using a computational molecular dynamics approach on a structure with the ion channel pore in a presumably open state. We determined that the region selecting between cations is the simplest of any channel of this type. Distinct from ion channels that select single ion species, cations are never fully dehydrated and have only one major ion binding site in the filter. Simulations suggested two similar binding sites for caesium, and studies of AMPARs in mammalian cell membranes showed that this makes caesium more permeant than sodium.

Heterogeneous distribution of AMPA glutamate receptor subunits at the photoreceptor synapses of rodent retina

2001 ◽  
Vol 13 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Iris Hack ◽  
Moritz Frech ◽  
Oliver Dick ◽  
Leo Peichl ◽  
Johann Helmut Brandstatter
Keyword(s):  
Glutamate Receptor ◽  
Heterogeneous Distribution

In vivo evaluation of [11C]CNS-5161 as a use-dependent ligand for the NMDA glutamate receptor channel

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S595-S595 ◽  
Author(s):  
Wynne K Schiffer ◽  
Deborah Pareto-Onghena ◽  
HaiTao Wu ◽  
Kuo-Shyan Lin ◽  
Andrew R Gibbs ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
In Vivo Evaluation ◽  
Nmda Glutamate Receptor ◽  
Receptor Channel
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