Ca 2+ ‐permeable AMPA receptors and their auxiliary subunits in synaptic plasticity and disease

Autor: Stuart G. Cull-Candy, Mark Farrant
Rok vydání: 2021
Předmět:
0301 basic medicine
amyotrophic lateral sclerosis
Physiology
Protein subunit
cocaine
AMPA receptor
Biology
Neurotransmission
Synaptic Transmission
GSG1L
Symposium Review
03 medical and health sciences
Glutamatergic
0302 clinical medicine
TARPs
CKAMP44
medicine
pain
Receptors
AMPA
Fear conditioning
neurological disorder
AMPA receptors
stargazin
calcium‐permeable AMPA receptors
Neurons
cornichon
synaptic plasticity
Neuronal Plasticity
musculoskeletal
neural
and ocular physiology
anoxia
malignant glioma
Motor neuron
fear conditioning
auxiliary subunits
ionotropic glutamate receptors
GluA2
030104 developmental biology
medicine.anatomical_structure
nervous system
Synaptic plasticity
Excitatory postsynaptic potential
Symposium Section Reviews: Ligand‐gated Ion Channels from Atomic Structure to Synaptic Transmission
Calcium Channels
Neuroscience
030217 neurology & neurosurgery
Zdroj: The Journal of Physiology
ISSN: 1469-7793
0022-3751
DOI: 10.1113/jp279029
Popis: AMPA receptors are tetrameric glutamate‐gated ion channels that mediate a majority of fast excitatory neurotransmission in the brain. They exist as calcium‐impermeable (CI‐) and calcium‐permeable (CP‐) subtypes, the latter of which lacks the GluA2 subunit. CP‐AMPARs display an array of distinctive biophysical and pharmacological properties that allow them to be functionally identified. This has revealed that they play crucial roles in diverse forms of central synaptic plasticity. Here we summarise the functional hallmarks of CP‐AMPARs and describe how these are modified by the presence of auxiliary subunits that have emerged as pivotal regulators of AMPARs. A lasting change in the prevalence of GluA2‐containing AMPARs, and hence in the fraction of CP‐AMPARs, is a feature in many maladaptive forms of synaptic plasticity and neurological disorders. These include modifications of glutamatergic transmission induced by inflammatory pain, fear conditioning, cocaine exposure, and anoxia‐induced damage in neurons and glia. Furthermore, defective RNA editing of GluA2 can cause altered expression of CP‐AMPARs and is implicated in motor neuron damage (amyotrophic lateral sclerosis) and the proliferation of cells in malignant gliomas. A number of the players involved in CP‐AMPAR regulation have been identified, providing useful insight into interventions that may prevent the aberrant CP‐AMPAR expression. Furthermore, recent molecular and pharmacological developments, particularly the discovery of TARP subtype‐selective drugs, offer the exciting potential to modify some of the harmful effects of increased CP‐AMPAR prevalence in a brain region‐specific manner.
figure legend AMPARs containing GluA2 (red subunits) are Ca2+‐impermeable (CI‐AMPARs). Those that lack GluA2 are Ca2+‐permeable (CP‐AMPARs) and are implicated in diverse forms of synaptic plasticity and disease. Both native CP‐ and CI‐AMPARs contain various auxiliary subunits (shown as yellow, green or turquoise) that affect AMPAR function and play a role in the regulation of relative CP‐/CI‐AMPAR prevalence. Image based on PDB model 6NJM.
Databáze: OpenAIRE
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