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J Neurosci
2011 May 18;3120:7511-20. doi: 10.1523/JNEUROSCI.6688-10.2011.
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Probing TARP modulation of AMPA receptor conductance with polyamine toxins.
Jackson AC
,
Milstein AD
,
Soto D
,
Farrant M
,
Cull-Candy SG
,
Nicoll RA
.
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The properties of synaptic AMPA receptors (AMPARs) depend on their subunit composition and association with transmembrane AMPAR regulatory proteins (TARPs). Although both GluA2 incorporation and TARP association have been shown to influence AMPAR channel conductance, the manner in which different TARPs modulate the mean channel conductance of GluA2-containing AMPARs is unknown. Using ultrafast agonist application and nonstationary fluctuation analysis, we found that TARP subtypes differentially increase the mean channel conductance, but not the peak open probability, of recombinant GluA2-containing AMPARs. TARP γ-8, in particular, enhances mean channel conductance to a greater degree than γ-2, γ-3, or γ-4. We then examined the action of a use-dependent antagonist of GluA2-containing AMPARs, philanthotoxin-74 (PhTx-74), on recombinant AMPARs and on GluA2-containing AMPARs in cerebellar granule neurons from stargazer mice transfected with TARPs. We found that the rate and extent of channel block varies with TARP subtype, in a manner that correlates linearly with mean channel conductance. Furthermore, block of GluA2-containing AMPARs by polyamine toxins varied depending on whether channels were activated by the full agonist glutamate or the partial agonist kainate, consistent with conductance state-dependent block. Block of GluA2-lacking AMPARs by PhTx-433 is also modulated by TARP association and is a function of agonist efficacy. Our data indicate that channel block by polyamine toxins is sensitive to the mean channel conductance of AMPARs, which varies with TARP subtype and agonist efficacy. Furthermore, our results illustrate the utility of polyamine toxins as sensitive probes of AMPAR channel conductance and suggest the possibility that TARPs may influence their channel properties by selectively stabilizing specific channel conformations, rather than altering the pore structure.
Andersen,
Uncompetitive antagonism of AMPA receptors: Mechanistic insights from studies of polyamine toxin derivatives.
2006, Pubmed,
Xenbase
Andersen,
Uncompetitive antagonism of AMPA receptors: Mechanistic insights from studies of polyamine toxin derivatives.
2006,
Pubmed
,
Xenbase
Ascher,
Quisqualate- and kainate-activated channels in mouse central neurones in culture.
1988,
Pubmed
Ayalon,
Functional assembly of AMPA and kainate receptors is mediated by several discrete protein-protein interactions.
2001,
Pubmed
,
Xenbase
Benke,
Modulation of AMPA receptor unitary conductance by synaptic activity.
1998,
Pubmed
Blaschke,
A single amino acid determines the subunit-specific spider toxin block of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor channels.
1993,
Pubmed
,
Xenbase
Bowie,
Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block.
1995,
Pubmed
Bowie,
Activity-dependent modulation of glutamate receptors by polyamines.
1998,
Pubmed
Brackley,
Selective antagonism of native and cloned kainate and NMDA receptors by polyamine-containing toxins.
1993,
Pubmed
,
Xenbase
Bredt,
AMPA receptor trafficking at excitatory synapses.
2003,
Pubmed
Burgess,
A cluster of three novel Ca2+ channel gamma subunit genes on chromosome 19q13.4: evolution and expression profile of the gamma subunit gene family.
2001,
Pubmed
Burnashev,
Control by asparagine residues of calcium permeability and magnesium blockade in the NMDA receptor.
1992,
Pubmed
,
Xenbase
Bähring,
An analysis of philanthotoxin block for recombinant rat GluR6(Q) glutamate receptor channels.
1998,
Pubmed
Bähring,
Permeation and block of rat GluR6 glutamate receptor channels by internal and external polyamines.
1997,
Pubmed
Chen,
Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms.
,
Pubmed
Cho,
Two families of TARP isoforms that have distinct effects on the kinetic properties of AMPA receptors and synaptic currents.
2007,
Pubmed
Coombs,
Transmembrane AMPA receptor regulatory proteins and AMPA receptor function in the cerebellum.
2009,
Pubmed
Cull-Candy,
Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons.
,
Pubmed
Cull-Candy,
Regulation of Ca2+-permeable AMPA receptors: synaptic plasticity and beyond.
2006,
Pubmed
Derkach,
Ca2+/calmodulin-kinase II enhances channel conductance of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors.
1999,
Pubmed
Fucile,
Effects of cyclothiazide on GluR1/AMPA receptors.
2006,
Pubmed
Gebhardt,
Influence of agonist concentration on AMPA and kainate channels in CA1 pyramidal cells in rat hippocampal slices.
2006,
Pubmed
Greger,
Molecular determinants of AMPA receptor subunit assembly.
2007,
Pubmed
Herlitze,
Argiotoxin detects molecular differences in AMPA receptor channels.
1993,
Pubmed
,
Xenbase
Hollmann,
Ca2+ permeability of KA-AMPA--gated glutamate receptor channels depends on subunit composition.
1991,
Pubmed
,
Xenbase
Isaac,
The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity.
2007,
Pubmed
Jackson,
Stargazin (TARP gamma-2) is required for compartment-specific AMPA receptor trafficking and synaptic plasticity in cerebellar stellate cells.
2011,
Pubmed
Jackson,
The expanding social network of ionotropic glutamate receptors: TARPs and other transmembrane auxiliary subunits.
2011,
Pubmed
Jahr,
Glutamate activates multiple single channel conductances in hippocampal neurons.
,
Pubmed
Jin,
Structural basis for partial agonist action at ionotropic glutamate receptors.
2003,
Pubmed
,
Xenbase
Jonas,
Quantal components of unitary EPSCs at the mossy fibre synapse on CA3 pyramidal cells of rat hippocampus.
1993,
Pubmed
Kamboj,
Intracellular spermine confers rectification on rat calcium-permeable AMPA and kainate receptors.
1995,
Pubmed
Kato,
AMPA receptor subunit-specific regulation by a distinct family of type II TARPs.
2008,
Pubmed
Kato,
New transmembrane AMPA receptor regulatory protein isoform, gamma-7, differentially regulates AMPA receptors.
2007,
Pubmed
Kim,
Assembly and stoichiometry of the AMPA receptor and transmembrane AMPA receptor regulatory protein complex.
2010,
Pubmed
,
Xenbase
Klugbauer,
A family of gamma-like calcium channel subunits.
2000,
Pubmed
Koh,
Block of native Ca(2+)-permeable AMPA receptors in rat brain by intracellular polyamines generates double rectification.
1995,
Pubmed
Kott,
Comparative analysis of the pharmacology of GluR1 in complex with transmembrane AMPA receptor regulatory proteins gamma2, gamma3, gamma4, and gamma8.
2009,
Pubmed
,
Xenbase
Kromann,
Solid-phase synthesis of polyamine toxin analogues: potent and selective antagonists of Ca2+-permeable AMPA receptors.
2002,
Pubmed
,
Xenbase
Lu,
Subunit composition of synaptic AMPA receptors revealed by a single-cell genetic approach.
2009,
Pubmed
Malinow,
AMPA receptor trafficking and synaptic plasticity.
2002,
Pubmed
Menuz,
TARP auxiliary subunits switch AMPA receptor antagonists into partial agonists.
2007,
Pubmed
Milstein,
TARP subtypes differentially and dose-dependently control synaptic AMPA receptor gating.
2007,
Pubmed
Milstein,
Regulation of AMPA receptor gating and pharmacology by TARP auxiliary subunits.
2008,
Pubmed
Milstein,
TARP modulation of synaptic AMPA receptor trafficking and gating depends on multiple intracellular domains.
2009,
Pubmed
Mosbacher,
A molecular determinant for submillisecond desensitization in glutamate receptors.
1994,
Pubmed
,
Xenbase
Nicoll,
Auxiliary subunits assist AMPA-type glutamate receptors.
2006,
Pubmed
Nilsen,
A subtype-selective, use-dependent inhibitor of native AMPA receptors.
2007,
Pubmed
Panchenko,
Amino acid substitutions in the pore of rat glutamate receptors at sites influencing block by polyamines.
1999,
Pubmed
,
Xenbase
Partin,
Structural determinants of allosteric regulation in alternatively spliced AMPA receptors.
1995,
Pubmed
,
Xenbase
Priel,
Block of kainate receptor desensitization uncovers a key trafficking checkpoint.
2006,
Pubmed
,
Xenbase
Prieto,
Gating modes in AMPA receptors.
2010,
Pubmed
Robinson,
Nonstationary fluctuation analysis and direct resolution of single channel currents at postsynaptic sites.
1991,
Pubmed
Rosenmund,
The tetrameric structure of a glutamate receptor channel.
1998,
Pubmed
Sager,
Functional modulation of AMPA receptors by transmembrane AMPA receptor regulatory proteins.
2009,
Pubmed
Shi,
The stoichiometry of AMPA receptors and TARPs varies by neuronal cell type.
2009,
Pubmed
Sigworth,
The variance of sodium current fluctuations at the node of Ranvier.
1980,
Pubmed
Smith,
Concentration-dependent substate behavior of native AMPA receptors.
2000,
Pubmed
Sobolevsky,
X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor.
2009,
Pubmed
Sommer,
RNA editing in brain controls a determinant of ion flow in glutamate-gated channels.
1991,
Pubmed
Soto,
Stargazin attenuates intracellular polyamine block of calcium-permeable AMPA receptors.
2007,
Pubmed
Soto,
Selective regulation of long-form calcium-permeable AMPA receptors by an atypical TARP, gamma-5.
2009,
Pubmed
Strømgaard,
AMPA receptor ligands: synthetic and pharmacological studies of polyamines and polyamine toxins.
2004,
Pubmed
Strømgaard,
Polyamine toxins: development of selective ligands for ionotropic receptors.
2005,
Pubmed
Suzuki,
The fast kinetics of AMPA GluR3 receptors is selectively modulated by the TARPs gamma 4 and gamma 8.
2008,
Pubmed
Swanson,
Single-channel properties of recombinant AMPA receptors depend on RNA editing, splice variation, and subunit composition.
1997,
Pubmed
Tikhonov,
Ion channels of glutamate receptors: structural modeling.
2007,
Pubmed
Tomita,
Functional studies and distribution define a family of transmembrane AMPA receptor regulatory proteins.
2003,
Pubmed
Tomita,
Stargazin modulates AMPA receptor gating and trafficking by distinct domains.
2005,
Pubmed
,
Xenbase
Traynelis,
Estimated conductance of glutamate receptor channels activated during EPSCs at the cerebellar mossy fiber-granule cell synapse.
1993,
Pubmed
Traynelis,
Glutamate receptor ion channels: structure, regulation, and function.
2010,
Pubmed
Turetsky,
Stargazin modulates native AMPA receptor functional properties by two distinct mechanisms.
2005,
Pubmed
Tóth,
Afferent-specific innervation of two distinct AMPA receptor subtypes on single hippocampal interneurons.
1998,
Pubmed
Washburn,
Block of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by polyamines and polyamine toxins.
1996,
Pubmed
,
Xenbase
Washburn,
Differential dependence on GluR2 expression of three characteristic features of AMPA receptors.
1997,
Pubmed
,
Xenbase
Zhang,
Structural and single-channel results indicate that the rates of ligand binding domain closing and opening directly impact AMPA receptor gating.
2008,
Pubmed
Zhang,
The relationship between agonist potency and AMPA receptor kinetics.
2006,
Pubmed
Ziff,
TARPs and the AMPA receptor trafficking paradox.
2007,
Pubmed