Glutathione and Glutathione Derivatives: Possible Modulators of Ionotropic Glutamate Receptors
Christopher A. Shaw in Glutathione in the Nervous System, 2018
The ionotropic AMPA receptors are activated by AMPA, quisqualate, and glutamate. Kainate, the most potent activator of the kainate receptors, also cross-reacts with AMPA receptors, though less effectively. The AMPA and kainate receptors are inhibited by 6,7-dinitroquinoxaline-2,3-dione (DNQX), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and sulfamoylbenzo(f)quinoxaline (NBQX) and are coupled to channels highly permeable to Na+ and K+ and much less permeable to Ca2+. An activation of these receptors increases the membrane permeability for these ions, accompanied by rapid depolarization (Récasens et al. 1992). They are thus primarily responsible for the fast excitatory glutamate transmission and neuronal-glial interaction. The colocalization of NMDA and AMPA sites (reviewed in Nicoll, Malenka, and Kauer 1990) may be of significance in the repetitive activation of NMDA receptors and in the generation of long-term potentiation (LTP). The kainate receptors may function as autoreceptors, since they are located presynaptically. Their exact physiological role is not however known (Seeburg 1993).
Subtle Alterations in Glutamatergic Synapses Underlie the Aging-Related Decline in Hippocampal Function
David R. Riddle in Brain Aging, 2007
AMPA receptors are composed of GluR1–4 subunits. In this class of glutamate receptors, GluR2 is the organizing subunit that is critical for AMPA receptor assembly and expression [79]. GluR2 also renders AMPA receptors more resistant to excitotoxicity in response to biological challenge by decreasing Ca2+ permeability [79–82]. The GluR1 subunit is essential for the formation of heteromeric AMPA receptors, which demonstrate higher conductance capacity compared to homomeric receptors formed by GluR2 alone [80–82]. In contrast with the relatively slow kinetics of the NMDA receptors, AMPA receptor activation accounts for fast postsynaptic responses [83, 84]. Compelling electrophysiological evidence indicates that the number of postsynaptic AMPA receptors is a major determinant of synaptic efficacy [85–87].
Tinnitus and Hyperacusis
John C Watkinson, Raymond W Clarke, Christopher P Aldren, Doris-Eva Bamiou, Raymond W Clarke, Richard M Irving, Haytham Kubba, Shakeel R Saeed in Paediatrics, The Ear, Skull Base, 2018
Glutamate is the main excitatory neurotransmitter in the auditory system and several subgroups of glutamate receptor exist. AMPA receptors are the main receptors found on the auditory nerve fibres under the inner hair cells and are responsible for the fast transmission of information from the cochlea to the brain.39 However, glutamate in large quantities is toxic to nerve fibres. This effect, which can be observed following significant noise exposure, is mediated by AMPA.40 Another subgroup of glutamate receptors, NMDA receptors are also present in auditory nerve fibres though their function is still a matter of some speculation. It has been observed that pharmacological blockade of NMDA receptors can be protective against both salicylate-induced41 and noise-induced tinnitus in animal models.42 Although the evidence that glutamate receptors are directly implicated in the causation of tinnitus is at best circumstantial, they do offer a potential site for therapeutic intervention and this continues to be an active research area.
Spider toxins targeting ligand-gated ion channels
Published in Toxin Reviews, 2021
Olena Filchakova
AMPA receptors are tetramers made up from homo- or heteromeric assembly of GluA1–GluA4 subunits (Traynelis et al. 2010). GluA2 subunit is a unique because it determines the calcium permeability of the receptor. mRNA transcript of GluA2 subunit can undergo RNA editing by adenosine deaminase which converts adenosine to inosine in glutamine-encoding codon CAG (Hume et al. 1991, Higuchi et al. 1993). CIG codon is recognized by arginine-charged tRNA. Thus, Q is substituted by R within M2 region of GluA2. AMPA receptor that incorporates edited GluA2 subunit (containing R) becomes impermeant to divalent cations, including Ca2+ (Sommer et al. 1991, Kohler et al. 1993). AMPA receptors containing GluA1, unedited GluA2, GluA3, and GluA4, all of which possess Q in Q/R site of M2, are permeable to calcium (Jonas and Burnashev 1995, Burnashev et al. 1996). Besides Ca2+ permeability, Q/R site influences voltage-dependent block by cytoplasmic polyamines which determines channel rectification properties (Bowie and Mayer 1995, Kamboj et al. 1995).
The positive allosteric modulation of GABAA receptors mRNA in immature hippocampal rat neurons by midazolam affects receptor expression and induces apoptosis
Published in International Journal of Neuroscience, 2019
Barbara Sinner, Julia Steiner, Manuela Malsy, Bernhard M. Graf, Anika Bundscherer
AMPA receptor subunit profiles change profoundly during neuronal development. In early developmental stages, AMPA receptors contain mainly Ca2+-permeable GluA1 subunits. During maturation GluA1 subunit expression decreases and is gradually substituted by Ca2+-impermeable GluA2 subunits [30]. Our experiments revealed that the suppression of neuronal activity resulted in a dose-dependent increase in GluA1 subunit receptor expression. Several other studies showed that the suppression of synaptic activity increases synaptic AMPA GluA1 subunits [31]. The initial increase in AMPA receptors GluA1 subunit is in parallel with the recruitment of AMPA receptors to the active side of the synapses. Excessive Ca2+-entry through the Ca2+ permeable GluA1 subunit of the AMPA receptor induces apoptosis [31]. We observed that the increase in the GluA1 subunit expression was associated with an increase in the activation of the pro-apoptotic pathways.
Molecular Mechanisms Associated with the Benefits of Variable Practice in Motor Learning
Published in Journal of Motor Behavior, 2020
Tércio Apolinário-Souza, Ana Flávia Santos Almeida, Natália Lelis-Torres, Juliana Otoni Parma, Grace Schenatto Pereira, Guilherme Menezes Lage
For more than 40 years, behavioral studies have raised hypotheses regarding the benefits of variable practice to memory processes (Moxley, 1979; Shea & Morgan, 1979; Shea & Zimny, 1983). Recently, studies have been associating cortical areas and the memory processes related to variable practice (Tanaka, Honda, Hanakawa, & Cohen, 2010; Wymbs & Grafton, 2009). Altogether, these studies suggest that the benefits of variable practice are associated with the recruitment of areas involved in cognitive functions (Lage et al., 2015). Nonetheless, they did not assess the molecular changes resulting from the distinct recruitment that underpins the benefits of variable practice. As far as we know, the present study is the first to specifically investigate how the expression of the NMDA and AMPA receptors are associated with these benefits. Finally, we developed a new experimental paradigm to the study of practice schedules. Studies with animal models can be an alternative to investigate the processes underlying learning in different types of practice scheduling.
Related Knowledge Centers
- Ampa
- Central Nervous System
- Glutamic Acid
- Ionotropic Glutamate Receptor
- Nmda Receptor
- Synapse
- Cell Surface Receptor
- Ligand-Gated Ion Channel
- Kainate Receptor
- Quisqualic Acid