NR2 subunit‐dependence of NMDA receptor channel block by external Mg<sup>2+</sup>

Qian, Anqi; Buller, Amy L.; Johnson, Jon W.

doi:10.1113/jphysiol.2004.076737

Cited by 66 publications

(82 citation statements)

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“…Passive and active (five different ion channels: Na, KDR, KA, CaT, and HCN) properties of the model neuron were set to match several somatodendritic measurements from CA1 pyramidal neurons (15-17, 26, 30, 40-42). SEPs were modeled by incorporation and activation of GluN2D-and GluN2B-containing NMDA receptors (29,(43)(44)(45)(46), with receptor location spanning the somatoapical dendritic tree. (I and J) Somatic (brown) and corresponding dendritic (∼220 μm from the soma, yellow) SEP amplitudes recorded when fast sodium channels (NaF) were incorporated into the model without (I) or with (J) T-type calcium (CaT) channels.…”

Section: Methodsmentioning

confidence: 99%

Active dendrites regulate the impact of gliotransmission on rat hippocampal pyramidal neurons

Ashhad

Narayanan

2016

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

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An important consequence of gliotransmission, a signaling mechanism that involves glial release of active transmitter molecules, is its manifestation as N-methyl-D-aspartate receptor (NMDAR)-dependent slow inward currents in neurons. However, the intraneuronal spatial dynamics of these events or the role of active dendrites in regulating their amplitude and spatial spread have remained unexplored. Here, we used somatic and/or dendritic recordings from rat hippocampal pyramidal neurons and demonstrate that a majority of NMDAR-dependent spontaneous slow excitatory potentials (SEP) originate at dendritic locations and are significantly attenuated through their propagation across the neuronal arbor. We substantiated the astrocytic origin of SEPs through paired neuron-astrocyte recordings, where we found that specific infusion of inositol trisphosphate (InsP 3 ) into either distal or proximal astrocytes enhanced the amplitude and frequency of neuronal SEPs. Importantly, SEPs recorded after InsP 3 infusion into distal astrocytes exhibited significantly slower kinetics compared with those recorded after proximal infusion. Furthermore, using neuron-specific infusion of pharmacological agents and morphologically realistic conductance-based computational models, we demonstrate that dendritically expressed hyperpolarization-activated cyclic-nucleotide-gated (HCN) and transient potassium channels play critical roles in regulating the strength, kinetics, and compartmentalization of neuronal SEPs. Finally, through the application of subtypespecific receptor blockers during paired neuron-astrocyte recordings, we provide evidence that GluN2B-and GluN2D-containing NMDARs predominantly mediate perisomatic and dendritic SEPs, respectively. Our results unveil an important role for active dendrites in regulating the impact of gliotransmission on neurons and suggest astrocytes as a source of dendritic plateau potentials that have been implicated in localized plasticity and place cell formation.neuron-astrocyte interaction | NMDA receptors | HCN channels | transient potassium channels | plateau potentials G liotransmission, a signaling mechanism that involves glial release of active transmitter molecules, has been implicated in the regulation of several neurophysiological processes that include synaptogenesis, synaptic transmission and plasticity, neuronal excitability, and synchrony (1-3). An important consequence of gliotransmission is its manifestation as slow inward currents (SIC), events that are mediated by neuronal extrasynaptic N-methyl-D-aspartate receptors (NMDAR) and are concomitant to astrocytic calcium elevations (3-8). Although these well-studied events have provided us with important insights into tripartite neuron-astrocyte interactions (1-9), recordings of such SICs have focused predominantly on the soma despite the dendritic localization of a majority of synapses (10). Research over the past two decades has clearly established that dendritic processing critically contributes to neuronal physiology and is best assesse...

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Section: Methodsmentioning

confidence: 99%

Active dendrites regulate the impact of gliotransmission on rat hippocampal pyramidal neurons

Ashhad

Narayanan

2016

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

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“…HEK 293 or 293T cells were transiently transfected 18 -48 h after plating with cDNAs for rat NMDA receptor subunits (Buller and Monaghan, 1997): NR1-1a [GenBank accession number (GAN) X63255, in plasmid pcDM8] plus NR2A (GAN M91561, in plasmid pcDNA1) or NR2D (GAN L31612, in plasmid pcDM8). Enhanced green fluorescent protein (eGFP) cDNA was cotransfected as previously described (Qian et al, 2005). 293T cells were transfected using LipofectAMINE/PLUS reagents (Invitrogen) by adding to each dish 1 ml of serum-free medium containing 1 g of total DNA (1 eGFP to 3 NR1 to 6 NR2A or 2D), 5 l of LipofectAMINE, and 4 l of PLUS.…”

Section: Methodsmentioning

confidence: 99%

“…Whole-cell recordings were performed as previously described (Qian et al, 2002) Single-channel recording and analysis. Single-channel recording and analysis were performed as previously described (Qian et al, 2005). Outside-out patch recordings were performed at room temperature according to standard methods (Hamill et al, 1981).…”

Section: Methodsmentioning

confidence: 99%

“…Understanding permeant ion effects on Mg o 2ϩ inhibition of NR1/2D receptors, which play important physiological roles developmentally and in adults (Okabe et al, 1998;Bengzon et al, 1999;Hrabetova et al, 2000;Miyamoto et al, 2002; Thompson et al, 2002), would deepen insight into blocking mechanisms and their variation among NMDA receptor subtypes. We previously reported (Qian et al, 2005) that Mg o 2ϩ inhibits NR2A and NR2B subunit-containing NMDA receptors more effectively than NR1/2D receptors predominantly because Mg o 2ϩ unbinds more quickly from NR1/2D receptors. Here, we combined electrophysiological and modeling approaches to examine permeant ion effects on Mg o 2ϩ block of NR1/2D receptors.…”

Section: Introductionmentioning

confidence: 97%

“…Investigation of Mg o 2ϩ block has improved understanding of synaptic regulation, mechanisms of drug action, and channel structure and gating. Mg o 2ϩ inhibition of NMDA receptors varies with brain region and developmental stage because of differential NR2 subunit expression coupled with NR2 subunit dependence of Mg o 2ϩ inhibition (Kato and Yoshimura, 1993;Monyer et al, 1994;Momiyama et al, 1996;Qian et al, 2005). The degree and voltage dependence of Mg o 2ϩ inhibition are powerfully modulated by permeant ions (Antonov and Johnson, 1999;Zhu and Auerbach, 2001a,b;Qian et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Permeant Ion Effects on External Mg²⁺Block of NR1/2D NMDA Receptors

Qian¹,

Johnson²

2006

J. Neurosci.

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Involvement of the synapse‐specific zinc transporter ZnT3 in cadmium‐induced hippocampal neurotoxicity

Mimouna

Charpentier

Lebon

et al. 2019

Journal Cellular Physiology

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The present study examined the involvement of zinc (Zn)‐transporters (ZnT3) in cadmium (Cd)‐induced alterations of Zn homeostasis in rat hippocampal neurons. We treated primary rat hippocampal neurons for 24 or 48 hr with various concentrations of CdCl2 (0, 0.5, 5, 10, 25, or 50 μM) and/or ZnCl 2 (0, 10, 30, 50, 70, or 90 μM), using normal neuronal medium as control. By The CellTiter 96 ® Aqueous One Solution Cell Proliferation Assay (MTS; Promega, Madison, WI) assay and immunohistochemistry for cell death markers, 10 and 25 μM of Cd were found to be noncytotoxic doses, and both 30 and 90 μM of Zn as the best concentrations for cell proliferation. We tested these selected doses. Cd, at concentrations of 10 or 25 μM (and depending on the absence or presence of Zn), decreased the percentage of surviving cells. Cd‐induced neuronal death was either apoptotic or necrotic depending on dose, as indicated by 7‐AAD and/or annexin V labeling. At the molecular level, Cd exposure induced a decrease in hippocampal brain‐derived neurotrophic factor‐tropomyosin receptor kinase B (BDNF‐TrkB) and Erk1/2 signaling, a significant downregulation of the expression of learning‐ and memory‐related receptors and synaptic proteins such as the NMDAR NR2A subunit and PSD‐95, as well as the expression of the synapse‐specific vesicular Zn transporter ZnT3 in cultured hippocampal neurons. Zn supplementation, especially at the 30 μM concentration, led to partial or total protection against Cd neurotoxicity both with respect to the number of apoptotic cells and the expression of several genes. Interestingly, after knockdown of ZnT3 by small interfering RNA transfection, we did not find the restoration of the expression of this gene following Zn supplementation at 30 μM concentration. These data indicate the involvement of ZnT3 in the mechanism of Cd‐induced hippocampal neurotoxicity.

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NR2 subunit‐dependence of NMDA receptor channel block by external Mg²⁺

Abstract: 2+ o ). NMDA receptor channel block by Mg

Cited by 66 publications

References 65 publications

Active dendrites regulate the impact of gliotransmission on rat hippocampal pyramidal neurons

Active dendrites regulate the impact of gliotransmission on rat hippocampal pyramidal neurons

Permeant Ion Effects on External Mg²⁺Block of NR1/2D NMDA Receptors

Involvement of the synapse‐specific zinc transporter ZnT3 in cadmium‐induced hippocampal neurotoxicity

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NR2 subunit‐dependence of NMDA receptor channel block by external Mg2+

Abstract: 2+ o ). NMDA receptor channel block by Mg

Cited by 66 publications

References 65 publications

Active dendrites regulate the impact of gliotransmission on rat hippocampal pyramidal neurons

Active dendrites regulate the impact of gliotransmission on rat hippocampal pyramidal neurons

Permeant Ion Effects on External Mg2+Block of NR1/2D NMDA Receptors

Involvement of the synapse‐specific zinc transporter ZnT3 in cadmium‐induced hippocampal neurotoxicity

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NR2 subunit‐dependence of NMDA receptor channel block by external Mg²⁺

Permeant Ion Effects on External Mg²⁺Block of NR1/2D NMDA Receptors