Comparative analysis of the pharmacology of GluR1 in complex with transmembrane AMPA receptor regulatory proteins γ2, γ3, γ4, and γ8

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

doi:10.1016/j.neuroscience.2007.12.047

Cited by 48 publications

(49 citation statements)

References 42 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%

“…In general, our present observations that g-2 increases the potency of externally applied PhTX-74 at heteromeric AMPARs, but not at homomeric AMPARs, is in good agreement with previous findings (Kott et al, 2009;Jackson et al, 2011). AMPARs activate the ion channel into multiple subconductance states (Swanson et al, 1997).…”

Section: Characterization Of Philanthotoxins At Amparssupporting

confidence: 93%

“…Previous work has shown that TARPs modulate polyamine channel block differentially among AMPAR subtypes (Soto et al, 2007;Kott et al, 2009;Jackson et al, 2011). In general, our present observations that g-2 increases the potency of externally applied PhTX-74 at heteromeric AMPARs, but not at homomeric AMPARs, is in good agreement with previous findings (Kott et al, 2009;Jackson et al, 2011).…”

Section: Characterization Of Philanthotoxins At Amparssupporting

confidence: 93%

“…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: Characterization Of Philanthotoxins At Amparssupporting

confidence: 93%

Section: Characterization Of Philanthotoxins At Amparssupporting

confidence: 93%

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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“…CNIH2 also increases AMPAR single channel conductance similarly to TARPs. However, CNIHs differ from TARPs in that they only minimally increase the efficacy of the partial agonist kainate (7,9) and fail to convert the competitive antagonist CNQX into a partial agonist (18,22).…”

Section: Discussionmentioning

confidence: 99%

Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating

Shi¹,

Suh

Milstein

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

110

159

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Glutamate receptors of the AMPA subtype (AMPARs) mediate fast synaptic transmission in the brain. These ionotropic receptors rely on auxiliary subunits known as transmembrane AMPAR regulatory proteins (TARPs) for both trafficking and gating. Recently, a second family of AMPAR binding proteins, referred to as cornichons, were identified and also proposed to function as auxiliary subunits. Cornichons are transmembrane proteins that modulate AMPAR function in expression systems much like TARPs. In the present study we compare the role of cornichons in controlling AMPA receptor function in neurons and HEK cells to that of TARPs. Cornichons mimic some, but not all, of the actions of TARPs in HEK cells; their role in neurons, however, is more limited. Although expressed cornichons can affect the trafficking of AMPARs, they were not detected on the surface of neurons and failed to alter the kinetics of endogenous AMPARs. This neuronal role is more consistent with that of an endoplasmic reticulum (ER) chaperone rather than a bona fide auxiliary subunit.stargazin | synapse | auxiliary subunit | hippocampus

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Studying the Excitatory and Inhibitory Neurotransmissions with Spider Venoms

Liberato¹,

Santos²

2016

Spider Venoms

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Comparative analysis of the pharmacology of GluR1 in complex with transmembrane AMPA receptor regulatory proteins γ2, γ3, γ4, and γ8

Cited by 48 publications

References 42 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

Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating

Studying the Excitatory and Inhibitory Neurotransmissions with Spider Venoms

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