New developments in the molecular pharmacology of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate and kainate receptors

Fletcher, Emma; Lodge, David

doi:10.1016/0163-7258(96)00014-9

Cited by 130 publications

(81 citation statements)

References 202 publications

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“…Presynaptic KARs on MF-CA3 synapses may act by depolarizing the nerve terminals (6,8). It has also been proposed that they are Ca 2ϩ -permeable, because their action is blocked by philanthotoxin-433 [PhTx (29)] that selectively targets unedited Ca 2ϩ -permeable glutamate receptors (30). We therefore tested whether PhTx affected synaptic plasticity in GluR7 Ϫ/Ϫ mice.…”

Section: Subcellular Localization Coassembly and Properties Of Glurmentioning

confidence: 99%

GluR7 is an essential subunit of presynaptic kainate autoreceptors at hippocampal mossy fiber synapses

Pinheiro

Perrais

Coussen

et al. 2007

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

126

179

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Presynaptic ionotropic glutamate receptors are emerging as key players in the regulation of synaptic transmission. Here we identify GluR7, a kainate receptor (KAR) subunit with no known function in the brain, as an essential subunit of presynaptic autoreceptors that facilitate hippocampal mossy fiber synaptic transmission. GluR7 ؊/؊ mice display markedly reduced short-and long-term synaptic potentiation. Our data suggest that presynaptic KARs are GluR6/ GluR7 heteromers that coassemble and are localized within synapses. We show that recombinant GluR6/GluR7 KARs exhibit low sensitivity to glutamate, and we provide evidence that presynaptic KARs at mossy fiber synapses are likely activated by high concentrations of glutamate. Overall, from our data, we propose a model whereby presynaptic KARs are localized in the presynaptic active zone close to release sites, display low affinity for glutamate, are likely Ca 2؉ -permeable, are activated by single release events, and operate within a short time window to facilitate the subsequent release of glutamate.kainate receptors ͉ presynaptic glutamate receptors ͉ short-term plasticity ͉ synaptic plasticity

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Section: Subcellular Localization Coassembly and Properties Of Glurmentioning

confidence: 99%

GluR7 is an essential subunit of presynaptic kainate autoreceptors at hippocampal mossy fiber synapses

Pinheiro

Perrais

Coussen

et al. 2007

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

126

179

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“…AMPA receptors can also be gated by relatively large concentrations of KA (Boulter et al, 1990) which evokes non-desensitizing responses (Paternain et al, 1995;Fletcher & Lodge, 1996;Lerma, 1998). However, the action of KA on naturally expressed AMPA receptors has been shown to be associated with a very rapidly desensitizing component which can only be detected using a very rapid application system .…”

Section: Introductionmentioning

confidence: 99%

“…Recombinant AMPA receptors are preferentially activated by AMPA, which produces a characteristic desensitizing response (Burnashev, 1993;Fletcher & Lodge, 1996). AMPA receptors can also be gated by relatively large concentrations of KA (Boulter et al, 1990) which evokes non-desensitizing responses (Paternain et al, 1995;Fletcher & Lodge, 1996;Lerma, 1998).…”

Section: Introductionmentioning

confidence: 99%

Characteristics of AMPA receptor‐mediated responses of cultured cortical and spinal cord neurones and their correlation to the expression of glutamate receptor subunits, GluR1‐4

Dai

Egebjerg

Lambert

2001

British J Pharmacology

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1 Electrophysiological recordings have been used to characterize responses mediated by AMPA receptors expressed by cultured rat cortical and spinal cord neurones. The EC 50 values for AMPA were 17 and 11 mM, respectively. 2 Responses of cortical neurones to AMPA were inhibited competitively by NBQX (pK i =6.6). Lower concentrations of NBQX (41 mM) also potentiated the plateau responses of spinal cord neurones to AMPA, which could be attributed to a depression of desensitization to AMPA. 3 GYKI 52466 inhibited responses of spinal cord neurones to AMPA to about twice the extent of responses of cortical neurones. 4 Blockade of AMPA receptor desensitization by cyclothiazide (CTZ) potentiated responses of spinal cord neurones (6.8 fold) signi®cantly more than responses of cortical neurones (4.8 fold). Responses of cortical neurones to KA were potentiated 3.5 fold by CTZ, while responses of spinal cord neurones were unaected. 5 Ultra-fast applications of AMPA to outside-out patches showed responses of spinal cord neurones desensitized by 97.5% and exhibit marked inward recti®cation, whereas cortical neurones desensitized by 91% and exhibited slight outward recti®cation. The time constants of deactivation and desensitization were about twice as fast in spinal cord than cortical neurones. 6 In cortical neurones, single-cell RT ± PCR showed GluR2 and GluR1 accounted for 91% of all subunits and were expressed together in 67% of neurones, predominantly as the¯ip variants (78%). GluR2 was detected alone in 24% of neurones. GluR3 and GluR4 were present in only 14 and 29% of neurones, respectively. For spinal cord neurones, GluR4 o was detected in 81% of neurones, whereas predominantly¯op versions of GluR1, 2 and 3 were detected in 38, 13 and 13% of neurones, respectively. These expression patterns are related to the respective pharmacological and mechanistic properties.

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“…7C,D). Since GluK1 receptors are known to be highly permeable to calcium (Lauri et al, 2003;Scott et al, 2008), in another set of experiments we applied PhTx (3 M), which blocks calciumpermeable AMPA/kainate receptor (Fletcher and Lodge, 1996). As UBP 302, PhTx significantly reduced the number of successes from 0.59 Ϯ 0.04 to 0.15 Ϯ 0.05 (n ϭ 7; p ϭ 0.001) (Fig.…”

Section: Activation Of Presynaptic Kainate Receptors Enhances Mf Excimentioning

confidence: 99%

In the Developing Rat Hippocampus, Endogenous Activation of Presynaptic Kainate Receptors Reduces GABA Release from Mossy Fiber Terminals

Caiati¹,

Sivakumaran²,

Cherubini³

2010

J. Neurosci.

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New developments in the molecular pharmacology of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate and kainate receptors

Cited by 130 publications

References 202 publications

GluR7 is an essential subunit of presynaptic kainate autoreceptors at hippocampal mossy fiber synapses

GluR7 is an essential subunit of presynaptic kainate autoreceptors at hippocampal mossy fiber synapses

Characteristics of AMPA receptor‐mediated responses of cultured cortical and spinal cord neurones and their correlation to the expression of glutamate receptor subunits, GluR1‐4

In the Developing Rat Hippocampus, Endogenous Activation of Presynaptic Kainate Receptors Reduces GABA Release from Mossy Fiber Terminals

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