Functional modulation of AMPA receptors by transmembrane AMPA receptor regulatory proteins

Sager, Charlotte; Tapken, Daniel; Kott, Sabine; Hollmann, Michael

doi:10.1016/j.neuroscience.2007.12.046

Cited by 44 publications

(33 citation statements)

References 64 publications

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“…Therefore, determination of the KA-to-GLU (KA/ GLU) current response ratio provides a convenient and robust test for functional expression of AMPARs in complex with g-2 (Tomita et al, 2005;Kott et al, 2007Kott et al, , 2009Sager et al, 2009a;Shi et al, 2009). In corroboration of previous findings (Tomita et al, 2005;Turetsky et al, 2005;Kott et al, 2007Kott et al, , 2009Sager et al, 2009a;Shi et al, 2009), we found that coexpression of g-2 increased the KA/GLU ratio more than 20-fold, from ∼1 to 25, for both homomeric GluA1 and GluA3 (Fig. 2, A and B).…”

Section: Resultssupporting

confidence: 89%

“…1, C and D, for a representative experiment (PhTX-74 at homomeric GluA1 expressed with g-2). For AMPAR subtypes coexpressed with g-2, we determined the ratio of steady-state currents evoked by GLU and the weak partial agonist KA as a test for functional expression and coassembly of g-2 with the AMPAR in oocytes (Tomita et al, 2005;Kott et al, 2007Kott et al, , 2009Sager et al, 2009a). AMPAR association with g-2 increases the receptor current response to KA relatively more than to GLU, resulting from changed AMPAR kinetics by the coassembly with g-2.…”

Section: Resultsmentioning

confidence: 99%

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Evaluation of PhTX-74 as Subtype-Selective Inhibitor of GluA2-Containing AMPA Receptors

et al. 2013

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The a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are glutamate-gated cation channels that mediate fast excitatory synaptic transmission in the central nervous system. AMPARs are tetramers formed by homo-or heteromeric assembly of GluA1-4 subunits to produce multiple subtypes with varying biophysical properties. Polyamine toxins such as joro spider toxins, philanthotoxins (PhTXs), and argiotoxins are use-dependent ion channel blockers of AMPARs widely employed as highly potent antagonists of GluA2-lacking receptor subtypes. In addition to this use, recent findings have indicated that a philanthotoxin analog, PhTX-74, can distinguish among GluA2-containing AMPAR subtypes in the presence of the prototypical transmembrane AMPAR regulatory protein g-2 (or stargazin). Thus, PhTX-74 may be of potential use in studies of the neurobiological role of GluA2-containing subtypes. We have evaluated the pharmacological profile of PhTX-74 and related polyamine toxins at homo-and heteromeric AMPARs in the presence and absence of g-2. Determination of IC 50 values for inhibition of glutamate-evoked currents from Xenopus oocytes expressing recombinant homo-or heteromeric combinations of GluA1, GluA2, and GluA3 in the presence of g-2 shows that PhTX-74 inhibits homomeric GluA1 and GluA3 receptors nonselectively, with IC 50 values in the nanomolar range (252-356 nM), and heteromeric GluA1/A2 and GluA2/A3 receptors nonselectively, with IC 50 values in the micromolar range (22 mM). Thus, in contrast to earlier findings, we find that PhTX-74 cannot pharmacologically discriminate between GluA2-containing AMPAR subtypes.

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Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Evaluation of PhTX-74 as Subtype-Selective Inhibitor of GluA2-Containing AMPA Receptors

et al. 2013

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“…A family of transmembrane proteins that closely associate with AMPARs (and may be considered auxiliary AMPAR subunits) is the transmembrane AMPAR regulatory protein (TARP) family, which includes γ2 (the first TARP identified, also called stargazin from the stargazer mutant mouse that lacks a functional version of this protein), γ3, γ4, and γ8 [305][306][307]. Two other more distant homologs, γ5 and γ7, have recently been suggested to constitute a type II family of TARPs [308].…”

Section: Iglur-interacting Proteinsmentioning

confidence: 99%

“…However, the relation between TARP-mediated trafficking of AMPARs and the subunit-specific trafficking of AMPARs that depends on the C-terminal tail of the different AMPAR subunits is unclear [309]. In addition to their role in receptor trafficking, TARPs strongly influence biophysical and pharmacological properties of AMPARs [305][306][307]. Knockdown of the TARP γ2 was observed to reduce the second, but not the first, phase of formalininduced nocifensive behavior, while acute nociception and locomotor function were unaffected [310].…”

Section: Iglur-interacting Proteinsmentioning

confidence: 99%

Ionotropic Glutamate Receptors in Spinal Nociceptive Processing

Larsson

2009

Mol Neurobiol

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Glutamate is the predominant excitatory transmitter used by primary afferent synapses and intrinsic neurons in the spinal cord dorsal horn. Accordingly, ionotropic glutamate receptors mediate basal spinal transmission of sensory, including nociceptive, information that is relayed to supraspinal centers. However, it has become gradually more evident that these receptors are also crucially involved in short- and long-term plasticity of spinal nociceptive transmission, and that such plasticity have an important role in the pain hypersensitivity that may result from tissue or nerve injury. This review will cover recent findings on pre- and postsynaptic regulation of synaptic function by ionotropic glutamate receptors in the dorsal horn and how such mechanisms contribute to acute and chronic pain.

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“…Stargazin has been reported to greatly enhance AMPA-receptormediated currents [25][26][27] and to additionally modulate several receptor properties. 25,26,[28][29][30][31][32][33] After coexpression of either XenGluR1(Q)flip, XenGluR2(R)flop, XenGluR3(Q)flop, or XenGluR4(Q)flop with stargazin, we found KA-induced currents of 13,543 ± 646 nA (n = 6), 552 ± 135 nA (n = 6), 385 ± 64 nA (n = 8), and 11,660 ± 606 nA (n = 6), respectively, with the homologous subunits from rat behaving similarly (data not shown). Thus, in the presence of stargazin, it was possible to perform a detailed characterization for every subunit.…”

Section: Homologous Receptor Subunits From Xenopus and Rat Show Similmentioning

confidence: 99%

Xenopus laevis Oocytes Endogenously Express All Subunits of the Ionotropic Glutamate Receptor Family

Schmidt¹,

Klein²,

Hollmann³

2009

Journal of Molecular Biology

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Functional modulation of AMPA receptors by transmembrane AMPA receptor regulatory proteins

Cited by 44 publications

References 64 publications

Evaluation of PhTX-74 as Subtype-Selective Inhibitor of GluA2-Containing AMPA Receptors

Evaluation of PhTX-74 as Subtype-Selective Inhibitor of GluA2-Containing AMPA Receptors

Ionotropic Glutamate Receptors in Spinal Nociceptive Processing

Xenopus laevis Oocytes Endogenously Express All Subunits of the Ionotropic Glutamate Receptor Family

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