Ca2+ signaling in postsynaptic neurons: Neuroplastin-65 regulates the interplay between plasma membrane Ca2+ ATPases and ionotropic glutamate receptors

Malci, Ayse; Lin, Xiao; Sandoval, Rodrigo; Gundelfinger, Eckart D.; Naumann, Michael; Seidenbecher, Constanze I.; Herrera-Molina, Rodrigo

doi:10.1016/j.ceca.2022.102623

Cited by 10 publications

(11 citation statements)

References 88 publications

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“…However, the link between the function of PMCA and iGluRs to regulate cytosolic Ca 2+ signaling remains unclear. Malci et al (2022) reported that Np65 coordinates the functions of PMCA and iGluRs to modulate the amplitude and duration of cytosolic Ca 2+ transitions in the dendrites and spines of hippocampal neurons. Malci et al (2022), using live-cell Ca 2+ imaging, acute pharmacological treatments, and GCaMP5G expression in hippocampal neurons, showed that endogenous or Np65-promoted PMCA activity contributes to the restoration of basal Ca 2+ levels and this effect is dependent on iGluR activation.…”

Section: Discussionmentioning

confidence: 99%

“…Black arrow shows immunoreactivity.revealed that electrical stimulation increased the number of synaptic neuroplastin-PMCA complexes due to iGluR activation, and low-rate overexpression of Np65 doubled PMCA levels and reduced cell surface levels of GluN2A and GluA1 in dendrites and Shank2-positive. In the same study, they observed decreased PMCA and unchanged GluN2B levels in neuroplastin-deficient hippocampi, whereas GluN2A and GluA1 levels were unbalanced Malci et al (2022). concluded that Np65 may interconnect PMCA with core players of the glutamatergic neurotransmission task to fine-tune Ca 2+ signaling regulation in basal synaptic function and plasticity(Malci et al, 2022) Herrera-Molina et al (2017).…”

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confidence: 91%

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Gender‐related variation expressions of neuroplastin TRAF6, GluA1, GABA(A) receptor, and PMCA in cortex, hippocampus, and brainstem in an experimental epilepsy model

Doğanyiğit,

Okan,

Yılmaz

et al. 2024

Synapse

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Epileptic seizures are seen as a result of changing excitability balance depending on the deterioration in synaptic plasticity in the brain. Neuroplastin, and its related molecules which are known to play a role in synaptic plasticity, neurotransmitter activities that provide balance of excitability and, different neurological diseases, have not been studied before in epilepsy.In this study, a total of 34 Sprague–Dawley male and female rats, 2 months old, weighing 250–300 g were used. The epilepsy model in rats was made via pentylenetetrazole (PTZ). After the completion of the experimental procedure, the brain tissue of the rats were taken and the histopathological changes in the hippocampus and cortex parts and the brain stem were investigated, as well as the immunoreactivity of the proteins related to the immunohistochemical methods.As a result of the histopathological evaluation, it was determined that neuron degeneration and the number of dilated blood vessels in the hippocampus, frontal cortex, and brain stem were higher in the PTZ status epilepticus (SE) groups than in the control groups. It was observed that neuroplastin and related proteins TNF receptor‐associated factor 6 (TRAF6), Gamma amino butyric acid type A receptors [(GABA(A)], and plasma membrane Ca2+ ATPase (PMCA) protein immunoreactivity levels increased especially in the male hippocampus, and only AMPA receptor subunit type 1 (GluA1) immunoreactivity decreased, unlike other proteins.We believe this may be caused by a problem in the mechanisms regulating the interaction of neuroplastin and GluA1 and may cause problems in synaptic plasticity in the experimental epilepsy model. It may be useful to elucidate this mechanism and target GluA1 when determining treatment strategies.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 91%

Gender‐related variation expressions of neuroplastin TRAF6, GluA1, GABA(A) receptor, and PMCA in cortex, hippocampus, and brainstem in an experimental epilepsy model

Doğanyiğit,

Okan,

Yılmaz

et al. 2024

Synapse

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“…Here, roughly 50% of the population motor output that drives breathing is generated through NMDARs (Fig 1), which means for every breath the animal takes, increases in intracellular Ca 2+ from NMDARs must be cleared to maintain ion homeostasis. Although the regulation of intracellular Ca 2+ is multifaceted, the plasma membrane Ca 2+ ATPase plays a large role in maintaining Ca 2+ homeostasis in active neurons (Malci et al, 2022; Schmidt et al, 2017). This pump consumes more than 3 times the ATP as the Na + /K + ATPase, as it extrudes 1 Ca 2+ ion per ATP hydrolyzed and transports Ca 2+ against a larger electrochemical gradient compared to Na + and K + .…”

Section: Discussionmentioning

confidence: 99%

Plasticity in the functional properties of NMDA receptors improves network stability during severe energy stress

Bueschke

Amaral-Silva

et al. 2023

Preprint

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Brain energy stress leads to neuronal hyperexcitability followed by a rapid loss of function and cell death. In contrast, the frog brain switches into a state of extreme metabolic resilience that allows them to maintain motor function during hypoxia as they emerge from hibernation. NMDA receptors (NMDARs) are Ca2+-permeable glutamate receptors that typically drive the loss of homeostasis during hypoxia. Therefore, we hypothesized that hibernation leads to plasticity that reduces the role of NMDARs within neural networks to improve function during energy stress. To test this, we assessed a circuit with a large involvement of NMDAR synapses, the brainstem respiratory network of female bullfrogs,Lithobates catesbieanus. Contrary to our expectations, hibernation did not alter the role of NMDARs in generating network output, nor did it affect the amplitude, kinetics, and hypoxia sensitivity of NMDAR currents. Instead, hibernation strongly reduced NMDAR Ca2+permeability and enhanced desensitization during repetitive stimulation, with shifts in mRNA copy number for NMDAR subunits that modify receptor function. Under severe hypoxia, the normal NMDAR profile caused network hyperexcitability within minutes, which was mitigated by blocking NMDARs. After hibernation, the modified complement of NMDARs protected against hyperexcitability, as disordered output did not occur for at least one hour in hypoxia. These findings uncover state-dependence in the plasticity of NMDARs, whereby distinct changes to receptor function improve neural performance during energy stress without interfering with its normal role during healthy activity.

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“…Similarly, the maxima and minima for

{([], {Ca}^{2 +})}_{s}

level is also sensitive to

v_{δ}

and

v_{β}

, the rates of IP 3 formation via PLCδ and PLCβ pathways, respectively. It is also known that the differences in cellular states in hippocampal neurons may arise from variability in expression levels of IP 3 R (Nakade et al, 1994), SERCA (Ludewig et al, 2021), L‐type VGCCs (Hirtz et al, 2011), and PMCA (Malci et al, 2022). The altered expression of PLCβ and PLCδ is also reported to be associated with neurological disorders (Dwivedi, 2002; Pandey et al, 2002).…”

Section: Methodsmentioning

confidence: 99%

A computational model to uncover the biophysical underpinnings of neural firing heterogeneity in dissociated hippocampal cultures

Dhyani,

George,

Gare

et al. 2023

Hippocampus

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Calcium (Ca2+) imaging reveals a variety of correlated firing in cultures of dissociated hippocampal neurons, pinpointing the non‐synaptic paracrine release of glutamate as a possible mediator for such firing patterns, although the biophysical underpinnings remain unknown. An intriguing possibility is that extracellular glutamate could bind metabotropic receptors linked with inositol trisphosphate (IP3) mediated release of Ca2+ from the endoplasmic reticulum of individual neurons, thereby modulating neural activity in combination with sarco/endoplasmic reticulum Ca2+ transport ATPase (SERCA) and voltage‐gated Ca2+ channels (VGCC). However, the possibility that such release may occur in different neuronal compartments and can be inherently stochastic poses challenges in the characterization of such interplay between various Ca2+ channels. Here we deploy biophysical modeling in association with Monte Carlo parameter sampling to characterize such interplay and successfully predict experimentally observed Ca2+ patterns. The results show that the neurotransmitter level at the plasma membrane is the extrinsic source of heterogeneity in somatic Ca2+ transients. Our analysis, in particular, identifies the origin of such heterogeneity to an intrinsic differentiation of hippocampal neurons in terms of multiple cellular properties pertaining to intracellular Ca2+ signaling, such as VGCC, IP3 receptor, and SERCA expression. In the future, the biophysical model and parameter estimation approach used in this study can be upgraded to predict the response of a system of interconnected neurons.

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Ca2+ signaling in postsynaptic neurons: Neuroplastin-65 regulates the interplay between plasma membrane Ca2+ ATPases and ionotropic glutamate receptors

Cited by 10 publications

References 88 publications

Gender‐related variation expressions of neuroplastin TRAF6, GluA1, GABA(A) receptor, and PMCA in cortex, hippocampus, and brainstem in an experimental epilepsy model

Gender‐related variation expressions of neuroplastin TRAF6, GluA1, GABA(A) receptor, and PMCA in cortex, hippocampus, and brainstem in an experimental epilepsy model

Plasticity in the functional properties of NMDA receptors improves network stability during severe energy stress

A computational model to uncover the biophysical underpinnings of neural firing heterogeneity in dissociated hippocampal cultures

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