Membrane Stretch Gates NMDA Receptors

Belin, Sophie; Maki, Bruce A.; Catlin, James; Rein, Benjamin; Popescu, Gabriela

doi:10.1523/jneurosci.0350-22.2022

Cited by 14 publications

(7 citation statements)

References 89 publications

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“… 58 A recent study has demonstrated that stretching plasma membrane can mechanically activate NMDAR independent of glutamate. 59 By counteracting swelling, active shrinkage prevents membrane stretching; thus, it may block a potential mechanically induced excitotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Active shrinkage protects neurons following axonal transection

Aydın,

Bay,

Yiğit

et al. 2023

iScience

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Section: Discussionmentioning

confidence: 99%

Active shrinkage protects neurons following axonal transection

Aydın,

Bay,

Yiğit

et al. 2023

iScience

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“…Interestingly, recent studies have confirmed that NMDAR is mechanically sensitive (Casado and Ascher, 1998 ; Belin et al, 2022 ). In the model of stretch-induced neuronal injury, the Mg 2+ blockage of the NMDAR channel significantly decreased and the NMDAR current increased (Zhang et al, 1996 ).…”

Section: Characteristics Of Nmdarsmentioning

confidence: 94%

NMDARs mediate peripheral and central sensitization contributing to chronic orofacial pain

Liu

Fang

et al. 2022

Front. Cell. Neurosci.

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Peripheral and central sensitizations of the trigeminal nervous system are the main mechanisms to promote the development and maintenance of chronic orofacial pain characterized by allodynia, hyperalgesia, and ectopic pain after trigeminal nerve injury or inflammation. Although the pathomechanisms of chronic orofacial pain are complex and not well known, sufficient clinical and preclinical evidence supports the contribution of the N-methyl-D-aspartate receptors (NMDARs, a subclass of ionotropic glutamate receptors) to the trigeminal nociceptive signal processing pathway under various pathological conditions. NMDARs not only have been implicated as a potential mediator of pain-related neuroplasticity in the peripheral nervous system (PNS) but also mediate excitatory synaptic transmission and synaptic plasticity in the central nervous system (CNS). In this review, we focus on the pivotal roles and mechanisms of NMDARs in the trigeminal nervous system under orofacial neuropathic and inflammatory pain. In particular, we summarize the types, components, and distribution of NMDARs in the trigeminal nervous system. Besides, we discuss the regulatory roles of neuron-nonneuronal cell/neuron-neuron communication mediated by NMDARs in the peripheral mechanisms of chronic orofacial pain following neuropathic injury and inflammation. Furthermore, we review the functional roles and mechanisms of NMDARs in the ascending and descending circuits under orofacial neuropathic and inflammatory pain conditions, which contribute to the central sensitization. These findings are not only relevant to understanding the underlying mechanisms, but also shed new light on the targeted therapy of chronic orofacial pain.

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“…Mechanosensitivity of NMDA receptors (an alternative opening to conventional glutamate induced activation) attracted growing interest recently [ 47 , 102 ]. In our search, among the two studies connecting NMDA receptors to migraine mechanical symptoms, one paper suggests that sec-butylpropylacetamide (SPD), a valproic acid derivative currently in use for migraine prophylaxis, is responsible for enhancing GABAergic transmission while reducing NMDA-mediated currents in cortical neurons [ 103 ].…”

Section: Methodsmentioning

confidence: 99%

Mechanosensitive receptors in migraine: a systematic review

Della Pietra,

Gómez Dabó,

Mikulenka

et al. 2024

J Headache Pain

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Background Migraine is a debilitating neurological disorder with pain profile, suggesting exaggerated mechanosensation. Mechanosensitive receptors of different families, which specifically respond to various mechanical stimuli, have gathered increasing attention due to their potential role in migraine related nociception. Understanding these mechanisms is of principal importance for improved therapeutic strategies. This systematic review comprehensively examines the involvement of mechanosensitive mechanisms in migraine pain pathways. Methods A systematic search across the Cochrane Library, Scopus, Web of Science, and Medline was conducted on 8th August 2023 for the period from 2000 to 2023, according to PRISMA guidelines. The review was constructed following a meticulous evaluation by two authors who independently applied rigorous inclusion criteria and quality assessments to the selected studies, upon which all authors collectively wrote the review. Results We identified 36 relevant studies with our analysis. Additionally, 3 more studies were selected by literature search. The 39 papers included in this systematic review cover the role of the putative mechanosensitive Piezo and K2P, as well as ASICs, NMDA, and TRP family of channels in the migraine pain cascade. The outcome of the available knowledge, including mainly preclinical animal models of migraine and few clinical studies, underscores the intricate relationship between mechanosensitive receptors and migraine pain symptoms. The review presents the mechanisms of activation of mechanosensitive receptors that may be involved in the generation of nociceptive signals and migraine associated clinical symptoms. The gender differences of targeting these receptors as potential therapeutic interventions are also acknowledged as well as the challenges related to respective drug development. Conclusions Overall, this analysis identified key molecular players and uncovered significant gaps in our understanding of mechanotransduction in migraine. This review offers a foundation for filling these gaps and suggests novel therapeutic options for migraine treatments based on achievements in the emerging field of mechano-neurobiology.

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Membrane Stretch Gates NMDA Receptors

Abstract: Membrane stretch gates NMDA receptor currents in the absence of neurotransmitter. Stretchgated currents have the biophysical hallmarks of the glutamate-gated currents including requirement for glycine, large Na + conductance, high Ca 2+ permeability, and voltage-dependent Mg 2+ block..

Cited by 14 publications

References 89 publications

Active shrinkage protects neurons following axonal transection

Active shrinkage protects neurons following axonal transection

NMDARs mediate peripheral and central sensitization contributing to chronic orofacial pain

Mechanosensitive receptors in migraine: a systematic review

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