Modulation of P2X7 purinergic receptor activity by extracellular Zn2+ in cultured mouse hippocampal astroglia

Kovács, Gergely; Környei, Zsuzsanna; Tóth, Krisztina; Baranyi, Mária; Brunner, János; Neubrandt, Máté; Sperlágh, Beáta

doi:10.1016/j.ceca.2018.07.010

Cited by 15 publications

(11 citation statements)

References 62 publications

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“…This difference may be associated with different methods used for CSD induction and the number of CSD induced in the two studies, i.e., immediate after CSD by KCl application in the present study versus the 5-min post multiple CSD by pinprick in mice [10]. Albeit PI is not a selective dye for Panx1 as the opening of large pore channels such as P2X7 receptors could also allow PI influx into neurons [25]; nevertheless, the CSD-induced PI influx in the rat cortex, at least in part, is attributed to the Panx1 channel opening. These data suggest that CSD is capable of promoting cortical Panx1 activation in the rat cortex.…”

Section: Discussionmentioning

confidence: 73%

Sarcoma Family Kinase-Dependent Pannexin-1 Activation after Cortical Spreading Depression Is Mediated by NR2A-Containing Receptors

Nie

Quinn

et al. 2020

IJMS

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Cortical spreading depression (CSD) is a propagating wave of depolarization followed by depression of cortical activity. CSD triggers neuroinflammation via the pannexin-1 (Panx1) channel opening, which may eventually cause migraine headaches. However, the regulatory mechanism of Panx1 is unknown. This study investigates whether sarcoma family kinases (SFK) are involved in transmitting CSD-induced Panx1 activation, which is mediated by the NR2A-containing N-methyl-D-aspartate receptor. CSD was induced by topical application of K+ to cerebral cortices of rats and mouse brain slices. SFK inhibitor, PP2, or NR2A–receptor antagonist, NVP–AAM077, was perfused into contralateral cerebral ventricles (i.c.v.) of rats prior to CSD induction. Co-immunoprecipitation and Western blot were used for detecting protein interactions, and histofluorescence for addressing Panx1 activation. The results demonstrated that PP2 attenuated CSD-induced Panx1 activation in rat ipsilateral cortices. Cortical susceptibility to CSD was reduced by PP2 in rats and by TAT-Panx308 that disrupts SFK–Panx1 interaction in mouse brain slices. Furthermore, CSD promoted activated SFK coupling with Panx1 in rat ipsilateral cortices. Moreover, inhibition of NR2A by NVP–AAM077 reduced elevation of ipsilateral SFK–Panx1 interaction, Panx1 activation induced by CSD and cortical susceptibility to CSD in rats. These data suggest NR2A-regulated, SFK-dependent Panx1 activity plays an important role in migraine aura pathogenesis.

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Section: Discussionmentioning

confidence: 73%

Sarcoma Family Kinase-Dependent Pannexin-1 Activation after Cortical Spreading Depression Is Mediated by NR2A-Containing Receptors

Nie

Quinn

et al. 2020

IJMS

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“…Using single-molecule tracking experiments and AMPAR immobilization techniques, Penn et al (2017) have shown that the surface movement of AMPARs is a key factor in the modulation of synaptic potentiation and learning ( Phan et al, 2015 ). At the molecular level, the recruitment and slow diffusion of glutamate receptors at the postsynaptic site have been shown after LTP ( Kovács et al, 2018 ). Indeed, our single-molecule tracking of hippocampal neurons demonstrated that cLTP decreased D AMPAR in synapses and increased the synaptic dwell time and content of GluR2-AMPARs.…”

Section: Discussionmentioning

confidence: 99%

“…Cells were triturated in Neurobasal (NB, Thermo Fisher Scientific) supplemented with B27 (Thermo Fisher Scientific), 5% FBS, 1% penicillin-streptomycin (Thermo Fisher Scientific). Then, 100.000 cells were plated on glass bottoms coated with poly-D-lysine (PDL)- and laminin-coated 35-mm glass-bottom dishes ( Kovács et al, 2018 ). Neurons were cultured in an incubator at 95% relative humidity and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Single-Molecule Imaging Reveals Rapid Estradiol Action on the Surface Movement of AMPA Receptors in Live Neurons

Godó

Barabás

Lengyel

et al. 2021

Front. Cell Dev. Biol.

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Gonadal steroid 17β-estradiol (E2) exerts rapid, non-genomic effects on neurons and strictly regulates learning and memory through altering glutamatergic neurotransmission and synaptic plasticity. However, its non-genomic effects on AMPARs are not well understood. Here, we analyzed the rapid effect of E2 on AMPARs using single-molecule tracking and super-resolution imaging techniques. We found that E2 rapidly decreased the surface movement of AMPAR via membrane G protein-coupled estrogen receptor 1 (GPER1) in neurites in a dose-dependent manner. The cortical actin network played a pivotal role in the GPER1 mediated effects of E2 on the surface mobility of AMPAR. E2 also decreased the surface movement of AMPAR both in synaptic and extrasynaptic regions on neurites and increased the synaptic dwell time of AMPARs. Our results provide evidence for understanding E2 action on neuronal plasticity and glutamatergic neurotransmission at the molecular level.

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“…2007), N‐methyl‐d‐aspartate (NMDA) receptors (Harrison & Gibbons, 1994), and purinergic receptor (Harrison & Gibbons, 1994; Kovacs et al. 2018). The influence of calcium on zinc is exemplified in calcium‐stimulated exocytotic events, resulting in extracellular zinc release from neurons (Frederickson & Bush, 2001) and pancreatic beta cells (Qian et al.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, zinc was found to directly increase the permeability of ryanodine receptors and release calcium from the sarcoplasmic reticulum in cardiomyocytes (Woodier et al 2015). Another mechanism by which zinc affects calcium is through modulating the gating of a variety of calcium permeable channels such as transient receptor potential ankyrin 1 (TRPA1) channel (Hu et al 2009), T-type voltage-gated calcium channels (VGCCs) (Traboulsie et al 2007), N-methyl-daspartate (NMDA) receptors (Harrison & Gibbons, 1994), and purinergic receptor (Harrison & Gibbons, 1994;Kovacs et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Spontaneous, synchronous zinc spikes oscillate with neural excitability and calcium spikes in primary hippocampal neuron culture

Zhang

Maslar

Minckley

et al. 2021

Journal of Neurochemistry

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Zinc has been suggested to act as an intracellular signaling molecule due to its regulatory effects on numerous protein targets including enzymes, transcription factors, ion channels, neurotrophic factors, and postsynaptic scaffolding proteins. However, intracellular zinc concentration is tightly maintained at steady levels under natural physiological conditions. Dynamic changes in intracellular zinc concentration have only been detected in certain types of cells that are exposed to pathologic stimuli or upon receptor ligand binding. Unlike calcium, the ubiquitous signaling metal ion that can oscillate periodically and spontaneously in various cells, spontaneous zinc oscillations have never been reported. In this work, we made the novel observation that the developing neurons generated spontaneous and synchronous zinc spikes in primary hippocampal cultures using a fluorescent zinc sensor, FluoZin‐3. Blocking of glutamate receptor‐dependent calcium influx depleted the zinc spikes, suggesting that these zinc spikes were driven by the glutamate‐mediated spontaneous neural excitability and calcium spikes that have been characterized in early developing neurons. Simultaneous imaging of calcium or pH together with zinc, we uncovered that a downward pH spike was evoked with each zinc spike and this transient cellular acidification occurred downstream of calcium spikes but upstream of zinc spikes. Our results suggest that spontaneous, synchronous zinc spikes were generated through calcium influx‐induced cellular acidification, which liberates zinc from intracellular zinc binding ligands. Given that changes in zinc concentration can modulate activities of proteins essential for synapse maturation and neuronal differentiation, these zinc spikes might act as important signaling roles in neuronal development.

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Modulation of P2X7 purinergic receptor activity by extracellular Zn2+ in cultured mouse hippocampal astroglia

Cited by 15 publications

References 62 publications

Sarcoma Family Kinase-Dependent Pannexin-1 Activation after Cortical Spreading Depression Is Mediated by NR2A-Containing Receptors

Sarcoma Family Kinase-Dependent Pannexin-1 Activation after Cortical Spreading Depression Is Mediated by NR2A-Containing Receptors

Single-Molecule Imaging Reveals Rapid Estradiol Action on the Surface Movement of AMPA Receptors in Live Neurons

Spontaneous, synchronous zinc spikes oscillate with neural excitability and calcium spikes in primary hippocampal neuron culture

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