Exam 2 - glutamate and GABA Flashcards
Glutamate/aspartate
principle excitatory NTs
Glutamate plays a specific functional role in
synaptic plasticity
What does the NMDA receptor not do?
it is not blocked by NBQX
Which drug does not enhance the effects of GABA on the GABAa receptor?
DBIs
Glutamate synthesis
- glutamate can be derived from metabolic breakdown of glucose
- precursor glutamine that uses catalyst enzyme glutaminase
These transporters are in charge of the release of glutamate:
- EAAT1-EAAT5
- EAAT1 and EAAT2 are located on astrocytes
What proteins are in charge of the reuptake of glutamate?
VGLUT1, 2, and 3
ALS results in the death of what kind of neurons?
glutamate
Glutamatergic system
- glutamate is used by all pyramidal neurons
- innervate the striatum, thalamus, and limbic system
- important for excitatory pathways
What is unique about the NMDA receptor?
- the only receptor that is both a sodium and calcium channel
- requires both glutamate and glycine or D-serine
- is an ionotropic receptor that also has secondary messenger characteristics
Ionotropic glutatmate receptors
- AMPA (sodium channel), Kainate (sodium channel), and NMDA (sodium and calcium channel)
- only receptors that causes depolarization
NBQX
- antagonist of AMPA and kainate receptors (glutamate receptors)
- causes sedation and reduced locomotor activity
- protects against induced seizures
Metabotropic glutamate receptors
- MGluR1-mGluR8
- some inhibit CAMP, others activate phosphoinositide second messenger system
MGluR1 receptor
important for locomotor activity, motor coordination, and learning
NMDA receptors play an important role in:
learning and memory
What is LTP and which receptor is important for LTP?
- long term potentiation
- NMDA
Doogie mouse
- overexpresses the NR2B subunit of the NMDA receptor
- shows enhanced LTP and better performance on morris water maze and novel object recognition task
Object recognition
subject has to remember which object is old and which is new, and will spend more time investigating the new object
Administering glutamate into a brain structure is (glutamate excitotoxicity)?
toxic, high concentrations cause cell death
Apoptosis
programmed cell death, cell shrivels up
Necrosis
cell death, cell swells and eventually explodes
Excitotoxicity in humans in exhibited when?
- ingesting domoic acid through seafood
- causes headache, dizziness, muscle weakness, mental confusion, and can result in death
Brain ischemia
disruption of blood supply to the brain
- focal - blockage in one area
- global - blockage to entire brain
- most damage is due to excess glutamate release
GABA and glycine
inhibitory NTs
GABA synthesis, what is synthesis blocked by?
- synthesized in a single step
- glutamate is the precursor, and GAD is the catalyst enzyme
- allylglycine - causes seizures
What is GABA loaded into vesicles by? What is it removed from the synaptic cleft by?
- VGAT
- GAT-1,2, and 3
GAT-1
- one of GABA’s receptors
- inhibitor is Tiagabine
- used to treat patients with epilepsy
- inhibition causes seizures
For every one GABA that is broken down, how many are made?
1
Where is GABA mainly found?
cerebral cortex, hippocampus, substantia nigra, and spinal cord
GABAa receptors
- has binding sites for all inhibitors
- ionotropic
- hyperpolarizing (chloride channel)
Muscimol
- GABAa agonist
- found in mushrooms, and have stimulatory and hallucinogenic qualities
- cause hyperthermia, altered appetite, repeated visions, similar effects to LSD
GABAa antagonists
- bicuculline and picrotoxin (non-competitive)
- both block the binding of GABA, causing seizures
Anxiolytic drugs
- antianxiety drugs with anticonvulsant properties (benzodiazepines)
- alcohol has similar properties to them
Seizures
random firing of neurons in the brain, consequence of interrupted GABA activity
Seizure disorders
brain disorder with an enduring predisposition to generate epileptic seizures
What are the two main types of seizures?
- generalized - involves entire brain
- partial - only a specific area of the brain is affected
What are the types of partial seizures?
- simple: motor or sensory, pt. remains conscious
- complex: impairment of consciousness, out of context behaviors (automatisms)
What are the types of generalized seizures?
- also called grand mal seizures, cause a change in consciousness
- tonic/clonic major convulsions, rigidity and jerks, loss of consciousness
- atonic: lapse of muscle tone
- myoclonic: brief jerks lasting not more than a second or two
- status epilepticus: series of seizures lasting >30 minutes, several grand mal seizures in a row, can cause damage to the hippocampus
Absence seizure
- petit mal seizures
- person appears to be staring into space with or without jerking or twitching movements
- common in children
How are seizures diagnosed?
- seizure type
- etiology
- age of onset
- EEG
- seizures associated with high amplitude spikes
Treatment of seizures
- anticonvulsants, which often act upon GABAa
- surgery in extreme cases
GABAb receptors
- inhibit CAMP formation and stimulate K+ channel opening
- common agonist is baclofen, which is given to patients with muscle spasticity
Drugs that act on the GABAa receptor can or cannot also act of the GABAb receptor?
cannot
