Glycine receptor heterogeneity in rat spinal cord during postnatal development.

Becker, Cord‐Michael; Hoch, Werner; Betz, Heinrich

doi:10.1002/j.1460-2075.1988.tb03255.x

Cited by 347 publications

(206 citation statements)

References 39 publications

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“…Immunofluorescence experiments were used to establish the efficiency and reversibility of drug application protocols, thus also ensuring their compatibility with neuron survival. We analyzed the GlyR ␣1-subunit, the predominant adult GlyR ␣-subunit isoform (Becker et al, 1988).…”

Section: Resultsmentioning

confidence: 99%

Cytoskeleton Regulation of Glycine Receptor Number at Synapses and Diffusion in the Plasma Membrane

et al. 2006

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Lateral diffusion of neurotransmitter receptors in and out of synapses has been postulated as a core mechanism for rapid changes in receptor number at synapses during plastic processes. In this study, we have used single particle tracking to investigate how changes in glycine receptor (GlyR) lateral diffusion properties might account for changes in receptor number at synapses after disruption of the cytoskeleton in dissociated spinal cord neurons. We found that pharmacological disruption of F-actin and microtubules decreased the amount of GlyR and gephyrin, the backbone of the inhibitory postsynaptic scaffold, at synapses. F-actin and microtubule disruption increased GlyR exchanges between the synaptic and extrasynaptic membranes and decreased receptor dwell time at synapses. GlyR lateral diffusion was predominantly controlled by microtubules in the extrasynaptic membrane and by actin at synapses. Both diffusion coefficients and confinement at synapses were affected after F-actin disruption. Our results indicate that receptor exchanges between the synaptic and extrasynaptic compartments depend on the properties of both the postsynaptic differentiation and the extrasynaptic membrane. Consequently, GlyR number at synapses may be rapidly modulated by the cytoskeleton through the regulation of lateral diffusion in the plasma membrane and of receptor stabilization at synapses.

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Section: Resultsmentioning

confidence: 99%

Cytoskeleton Regulation of Glycine Receptor Number at Synapses and Diffusion in the Plasma Membrane

et al. 2006

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“…Furthermore, the possibility exists that hippocampal neurons may express both ␣ homomeric receptors, the immature extrasynaptic GlyR subtype and ␣␤ heteromeric GlyRs, the mature form of the receptor that is synaptically located (Becker et al 1988;Kungel and Friauf 1997;Malosio et al 1991;Takahashi et al 1992). To pursue whether pyramidal cells and interneurons in acute slices at this stage of maturity express ␣ homomeric and/or ␣␤ heteromeric GlyRs, we tested whether the GABA A R antago-FIG.…”

Section: Hippocampal Glyrs Are Blocked By Picrotoxinmentioning

confidence: 99%

“…Native GlyRs in spinal cord and brain stem are either ␣ homomeric GlyRs (immature, extrasynaptic subtype) or ␣␤ heteromeric GlyRs (mature, synaptic subtype) (Becker et al 1988;Kungel and Friauf 1997;Malosio et al 1991;Takahashi et al 1992). Fortunately, the GABA A R antagonist picrotoxin is a useful tool in differentiating between homomeric and heteromeric GlyRs because the presence of the ␤ subunit in heteromeric receptors confers picrotoxin resistance (Pribilla et al 1992).…”

Section: Picrotoxin Antagonism Suggests Multiple Glyr Subtypesmentioning

confidence: 99%

“…Presumably these effects of taurine in hippocampus are mediated via activation of GlyRs; however, this mechanism has never been tested. In situ hybridization and immunohisto-chemical studies show that expression of GlyR subunits in hippocampus is developmentally regulated with expression continuing throughout adulthood, although at decreased levels compared with early postnatal stages (Becker et al 1993;Malosio et al 1991;Sato et al 1992). Powerful glycine transporters believed to be responsible for terminating glycinergic synaptic transmission in other regions of the CNS are present in hippocampus, with the GlyT1 subtype expressed by astrocytes and GlyT2 selectively expressed by neurons (Jursky and Nelson 1995;Zafra et al 1995aZafra et al ,b, 1997.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacological Characterization of Glycine-Gated Chloride Currents Recorded in Rat Hippocampal Slices

Chattipakorn

McMahon

2002

Journal of Neurophysiology

139

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Chattipakorn, Siriporn C. and Lori L. McMahon. Pharmacological characterization of glycine-gated chloride currents recorded in rat hippocampal slices. J Neurophysiol 87: 1515-1525, 2002; 10.1152/jn. 00365.2001. An inhibitory role for strychnine-sensitive glycine-gated chloride channels (GlyRs) in mature hippocampus has been overlooked, largely due to the misconception that GlyR expression ceases early during development and to few functional studies demonstrating their presence. As a result, little is known regarding the physiological and pharmacological properties of native GlyRs expressed by hippocampal neurons. In this study, we used pharmacological tools and whole cell patch-clamp recordings of CA1 pyramidal cells and interneurons in acutely prepared hippocampal slices from 3-to 4-wk old rats to characterize these understudied receptors. We show that glycine application to recorded pyramidal cells and interneurons elicited strychnine-sensitive chloride-mediated currents (I gly ) that did not completely desensitize in the continued presence of agonist but reached a steady state at 45-60% of the peak amplitude. Additionally, the inhibitory amino acid, taurine, which has been shown to activate GlyRs in other systems, activated GlyRs expressed by both pyramidal cells and interneurons, although with much less potency than glycine, having an EC 50 10-fold higher. To examine the potential subunit composition of hippocampal GlyRs, we tested the effect of the GABA A receptor antagonist, picrotoxin, on I gly recorded from both cell types. At low micromolar concentrations of picrotoxin (Յ100 M), which selectively block ␣ homomeric GlyRs, I gly was partially attenuated in both cell types, indicating that ␣ homomeric receptors are expressed by pyramidal cells and interneurons. At picrotoxin concentrations Յ1 mM, ϳ10 -20% of the whole cell current remained, suggesting that ␣␤ heteromeric GlyRs are also expressed because this subtype of GlyR is relatively resistant to picrotoxin antagonism. Finally, we examined whether hippocampal GlyRs are modulated by zinc. Consistent with previous reports in other preparations, zinc elicited a bidirectional modulation of GlyRs, with physiological zinc concentrations (1-100 M) increasing whole cell currents and concentrations Ͼ100 M depressing them. Furthermore, the same concentration of zinc that potentiates I gly suppressed currents mediated by the N-methyl-D-aspartate subtype of the glutamate receptor. Thus we provide a pharmacological characterization of native GlyRs expressed by both major neuron types in hippocampus and show that these receptors can be activated by taurine, an amino acid that is highly concentrated in hippocampus. Furthermore, our data suggest that at least two GlyR subtypes are present in hippocampus and that GlyR-mediated currents can be potentiated by zinc at concentrations that suppress glutamate-mediated excitability.

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“…We next examined whether the AMPAR subunits might switch during development like other ionotropic receptors (Mishina et al, 1986;Akagi and Miledi, 1988;Becker et al, 1988;Watanabe et al, 1992;Okada et al, 2000). After recording qEPSCs from MNTB neurons, intracellular contents were harvested into the patch pipette and submitted for the quantitative RT-PCR analysis (Lambolez et al, 1992).…”

Section: Developmental Change In the Ampar Subunit Transcriptsmentioning

confidence: 99%

Mechanisms Underlying Developmental Speeding in AMPA-EPSC Decay Time at the Calyx of Held

Koike-Tani

Saitoh²,

Takahashi³

2005

J. Neurosci.

116

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The time course of synaptic conductance is important in temporal precision of information processing in the neuronal network. The AMPA receptor (AMPAR)-mediated EPSCs at the calyx of Held become faster in decay time as animals mature. To clarify how desensitization and deactivation of AMPARs contribute to developmental speeding of EPSCs, we compared the decay time of quantal EPSCs (qEPSCs) with the deactivation and desensitization times of AMPAR currents induced in excised patches by fast glutamate application (AMPA patch currents). Both the deactivation and desensitization times of AMPA patch currents became markedly faster from postnatal day 7 (P7) to P14 and changed little thereafter. In individual neurons, throughout development (P7-P21), the time constants of deactivation and fast desensitization in AMPA patch currents were similar to each other and close to the qEPSC decay time constant. Cyclothiazide (CTZ) abolished the fast desensitization, prolonged deactivation of AMPA patch currents, and slowed the decay time of EPSCs. The effects of CTZ on AMPA patch currents were unchanged throughout development, whereas its effect on EPSCs became weaker as animals matured. In single-cell reverse transcription-PCR analysis, glutamate receptor subunit 4 (GluR4) flop increased from P7 to P14 and changed little thereafter. At P7, the GluR4 flop abundance had an inverse correlation with the qEPSC decay time. These results together suggest that both desensitization and deactivation of AMPARs are involved in the EPSC decay time, but the contribution of desensitization decreases during postnatal development at the calyx of Held.

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Glycine receptor heterogeneity in rat spinal cord during postnatal development.

Cited by 347 publications

References 39 publications

Cytoskeleton Regulation of Glycine Receptor Number at Synapses and Diffusion in the Plasma Membrane

Cytoskeleton Regulation of Glycine Receptor Number at Synapses and Diffusion in the Plasma Membrane

Pharmacological Characterization of Glycine-Gated Chloride Currents Recorded in Rat Hippocampal Slices

Mechanisms Underlying Developmental Speeding in AMPA-EPSC Decay Time at the Calyx of Held

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