Glutamate Flashcards
What is a neurotransmitter?
Describe the movement of the neurotransmitter
Neurotransmitters are chemical messengers that transmit signals from a neuron to a target cell across a synapse (i.e. neurotransmission).
- The molecule must be synthesised and stored in the pre-synaptic neuron
- The molecule must be released by the pre-synaptic axon terminal upon stimulation
- The molecule must produce a response in the post-synaptic cell
What is glutamate?
Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS).
Nearly all excitatory neurons in the CNS are glutamatergic and it has been estimated that over half of all brain synapses release glutamate
How is glutamate synthesised and stored?
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Describe the re-uptake and degradation of glutamate
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What are the 2 types of neurotransmitter receptors?
There are two broad families of neurotransmitter receptor – ligand-gated ion channels (ionotropic) and G-protein coupled receptors (metabotropic).
What are the 3 Ionotropic and metabotropic glutamate receptors?
What do these receptors allow in?
Ionotropic:
- AMPA receptors
- NMDA receptors
- Kainate receptors
Metabotropic:
• Group I
• Group II
• Group III
What are the 4 subunits of AMPA receptors?
Describe the structure of the receptor#
What prevents calcium ions entering?
Four subunit types (plus alternate splice variants):
- GluA1
- GluA2
- GluA3
- GluA4
Hetero-tetrameric - “Dimer of dimers”
• Four orthosteric binding sites
• Two sites must be occupied for channel opening
• Current increases as more binding sites are occupied
Most commonly:
• 2 GluA2 subunits
• 2 GluA1, 3 or 4
Presence of GluA2 subunits prevents Ca2+ flow
Describe the structure of the NMDA receptors
Three subunit types (plus alternate splice variants):
- GluN1 (or NR1)
- GluN2 (or NR2)
- GluN3 (or NR3)
Hetero-tetrameric
“Dimer of dimers”
Most commonly:
• 2 GluN1 subunits
Describe the structure of the Kainate receptors
Five subunit types (plus alternate splice variants):
- GluK1 (GluR5)
- GluK2 (GluR6)
- GluK3 (GluR7)
- GluK4 (KA1)
- GluK5 (KA2)
Tetrameric:
• GluK1-3 can form homomers or heteromers
• GluK4 & 5 only heteromers with GluK1-3 subunits
Ligand-gated ion channel: Glutamate binding required for channel opening – not particularly well understood
• Limited distribution in the brain compared to AMPA/NMDA receptors
Describe the structure of the metabotropic glutamate receptors
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What do Excitatory neurotransmitters (e.g. glutamate) lead to?
Excitatory neurotransmitters (e.g. glutamate) can lead to neuronal membrane depolarisation – displacement of a membrane potential towards a more positive value.
What is a The excitatory post-synaptic current (EPSC)?
What do they lead to?
Which receptors are faster and slower?
The excitatory post-synaptic current (EPSC) represents the flow of ions, and change in current, across a post-synaptic membrane.
• EPSCs lead to the generation of excitatory post synaptic potentials (EPSPs), which increase the likelihood of firing an action potential
• EPSCs produced by the NMDA receptor and kainate receptor are slower and last longer than those produced by AMPA receptors
What is Excitotoxicity?
Excitotoxicity is the pathological process by which excessive excitatory stimulation can lead to neuronal damage and death.
Excessive Ca2+ can cause: • Mitochondrial damage • Oxidative stress • Apoptosis Excitotoxicity linked to: • Stroke • Alzheimer’s disease…
Describe Glutamate-mediated excitotoxicity in Alzheimer’s disease
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What is Long-term potentiation (LTP)?
Long-term potentiation (LTP) refers to the persistent strengthening of a synapse based upon repeated patterns of activity.
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