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40 Cards in this Set

  • Front
  • Back
What enzyme synthesizes GABA and what does it do?
GAD (glutamic acid decarboxylase); removes carboxyl group from glutamate
What are the two isoforms of GAD?
GAD65, GAD67
Where is GAD highly concentrated?
axon terminals
What three drugs block GABA synthesis?
Allylglycine
Thiosemicarbazide
3-mercaptopropionic acid
How is synthesis regulated?
GABA separates the hooenzyme complex into apoenzyme GAD and pyridoxal phosphate
Is calcium required for GABA release from the synapse?
Not necessarily
What molecule takes up GABA back into astrocytes?
VGATs (vesicular GABA trasporters)
What are the two pools of GABA in a neuron?
NT pool
metabolic pool
What do GATs require to work?
extracellular Na+ and Cl- (it is a symporter)
Describe the GABA cycling process
GABA released into synaptic cleft

Astrocyte:
1. VGAT-1, VGAT-2, or VGAT-3 takes up into astrocyte
2. GABA-->glutamate-->glutamine
3. glutamine released from astrocyte
4. glutamine transported back into presynaptic cell via glutamine transporters
5. glutamine-->glutamate
6. GAD converts some glutamate into GABA to be released again

Back into presynaptic neuron:
1. GAT-1 takes in GABA
2a. GABA-->glutamate
2b. GABA-->succinate via GABA aminotransferase
2c. GABA-->vesicle
What does vigabatrin do?
blocks GABA aminotransferase, so GABA is not converted into succinate
What does tetanus do to GABA?
cleaves synaptobrevin (docks vesicles at active zone)
Two examples of GABAergic tracts
striatum-->globus pallidus (motor)
striatum-->substantia nigra ( - feedback)

(frontal cortex, GABA is just inhibitory inerneuron)
7 good examples of places that use GABA
hippocampus
cortex
substantia nigra
cerebellum
striatum
globus pallidus
olfactory bulbs
What are the two general types of GABA receptors, and which is which (metab/ion)?
A - ionotropic
B - metabotropic
What is an example of an ionotropic GABA-R agonist, and what are behavioral effects?
muscimol (in mushrooms)

macroscopia (seeing things bigger than they actually are)

hyperthermia
elevated mood
anorexia
dilated pupils
difficulty concentrating
ataxia
catalepsy
hallucinations
What is an example of an ionotropic GABA-R antagonist, and what are its behavioral effects?
bicuculline (competitive antagonist)

causes seizures
What are GABA A R agonists and antagonists good for?
turning "on" or "off" different brain areas
What are GABA A Rs permeable to?
Cl-
How many subunits are included in each GABA A R?
5
What are the 8 different families of GABA A subunits?
alpha (6)
beta (4)
gamma (3)
row (3)
delta
upsilon
theta
pi
What is the main consequence of GABA A R being Cl-ionophores?
inhibits AP
What are two different common arrangements of GABA A R subunits?
2 alpha, 2 beta, 1 gamma
2 alpha, 1 beta, 2 gamma
List five molecules that can bind a GABA A receptor
GABA
neurosteroid
BDZ (benzodiazepene)
barbiturate
picrotoxin (pentelynetetrazol/Metrazol)
What does a neurosteroid do when it binds a GABA A receptor?
it can either inhibit or facilitate receptor action
What causes convulsions when it binds GABA A receptors as a noncompetitive antagonist?
picrotoxin
aka methylenetetrazol
aka Metrazol
What does BDZ do on a GABA A receptor?
positive allosteric modulator

increases rate of channel opening

sedates/has hyponotic effects
relaxes muscles
is anti-convulsant
What are two examples of BZDs that bind GABA A receptors?
Valium (diazepam)
Librium (chlordiazepoxide)
What does a barbiturate do to a GABA A receptor?
positive allosteric modulator

increases mean open time of the channel

similar effects as BZD (decrease anxiety, anticonvulsant, muscle relaxer, sedates)
Where do common negative allosteric molecules bind on the GABA A receptor?
at the barbiturate site (antagonist)
What are the two parts of a GABA B receptor and what are they capable of binding?
B1 - binds GABA, not G protein
B2 - binds G protein, not GABA

form multimeric complexs!
What does the GABA B receptor do?
opens K+ channels
inhibits voltage-gated Ca2+ channels
inhibits adenylate cyclase
Are GABA B receptors autoreceptors or postsynaptic?
can be either
List 4 places were GABA B receptors are found
cerebellum
layers I-III cerebral cortex
superior colliculus
interpeduncular nucleus
What are two selective agonists of GABA B receptors and what do they do?
baclofen, saclofen

antispastic agents and muscle relaxants
What's a selective antagonist of GABA B?
phaclofen
List 8 roles of GABA in behavior
aggression
feeding
sexual behavior
mood
pain sensitivity
locomotor activity
cardiovascular regulation
thermoregulation
What are two things that epileptics have that hint that decreased GABA function
1. not as much GABA in CSF
2. less GAD when focusing (inconsistent though)
What has been shown to decrease convulsions? (and vice versa)
increasing GABA
How did Kindling model epilepsy?
decreased GAD
decreased GABA conc
alterations in GABA-R (binding and Cl- flux)