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40 Cards in this Set
- Front
- Back
What enzyme synthesizes GABA and what does it do?
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GAD (glutamic acid decarboxylase); removes carboxyl group from glutamate
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What are the two isoforms of GAD?
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GAD65, GAD67
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Where is GAD highly concentrated?
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axon terminals
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What three drugs block GABA synthesis?
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Allylglycine
Thiosemicarbazide 3-mercaptopropionic acid |
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How is synthesis regulated?
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GABA separates the hooenzyme complex into apoenzyme GAD and pyridoxal phosphate
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Is calcium required for GABA release from the synapse?
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Not necessarily
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What molecule takes up GABA back into astrocytes?
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VGATs (vesicular GABA trasporters)
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What are the two pools of GABA in a neuron?
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NT pool
metabolic pool |
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What do GATs require to work?
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extracellular Na+ and Cl- (it is a symporter)
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Describe the GABA cycling process
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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 |
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What does vigabatrin do?
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blocks GABA aminotransferase, so GABA is not converted into succinate
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What does tetanus do to GABA?
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cleaves synaptobrevin (docks vesicles at active zone)
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Two examples of GABAergic tracts
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striatum-->globus pallidus (motor)
striatum-->substantia nigra ( - feedback) (frontal cortex, GABA is just inhibitory inerneuron) |
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7 good examples of places that use GABA
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hippocampus
cortex substantia nigra cerebellum striatum globus pallidus olfactory bulbs |
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What are the two general types of GABA receptors, and which is which (metab/ion)?
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A - ionotropic
B - metabotropic |
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What is an example of an ionotropic GABA-R agonist, and what are behavioral effects?
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muscimol (in mushrooms)
macroscopia (seeing things bigger than they actually are) hyperthermia elevated mood anorexia dilated pupils difficulty concentrating ataxia catalepsy hallucinations |
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What is an example of an ionotropic GABA-R antagonist, and what are its behavioral effects?
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bicuculline (competitive antagonist)
causes seizures |
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What are GABA A R agonists and antagonists good for?
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turning "on" or "off" different brain areas
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What are GABA A Rs permeable to?
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Cl-
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How many subunits are included in each GABA A R?
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5
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What are the 8 different families of GABA A subunits?
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alpha (6)
beta (4) gamma (3) row (3) delta upsilon theta pi |
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What is the main consequence of GABA A R being Cl-ionophores?
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inhibits AP
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What are two different common arrangements of GABA A R subunits?
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2 alpha, 2 beta, 1 gamma
2 alpha, 1 beta, 2 gamma |
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List five molecules that can bind a GABA A receptor
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GABA
neurosteroid BDZ (benzodiazepene) barbiturate picrotoxin (pentelynetetrazol/Metrazol) |
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What does a neurosteroid do when it binds a GABA A receptor?
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it can either inhibit or facilitate receptor action
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What causes convulsions when it binds GABA A receptors as a noncompetitive antagonist?
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picrotoxin
aka methylenetetrazol aka Metrazol |
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What does BDZ do on a GABA A receptor?
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positive allosteric modulator
increases rate of channel opening sedates/has hyponotic effects relaxes muscles is anti-convulsant |
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What are two examples of BZDs that bind GABA A receptors?
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Valium (diazepam)
Librium (chlordiazepoxide) |
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What does a barbiturate do to a GABA A receptor?
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positive allosteric modulator
increases mean open time of the channel similar effects as BZD (decrease anxiety, anticonvulsant, muscle relaxer, sedates) |
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Where do common negative allosteric molecules bind on the GABA A receptor?
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at the barbiturate site (antagonist)
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What are the two parts of a GABA B receptor and what are they capable of binding?
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B1 - binds GABA, not G protein
B2 - binds G protein, not GABA form multimeric complexs! |
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What does the GABA B receptor do?
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opens K+ channels
inhibits voltage-gated Ca2+ channels inhibits adenylate cyclase |
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Are GABA B receptors autoreceptors or postsynaptic?
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can be either
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List 4 places were GABA B receptors are found
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cerebellum
layers I-III cerebral cortex superior colliculus interpeduncular nucleus |
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What are two selective agonists of GABA B receptors and what do they do?
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baclofen, saclofen
antispastic agents and muscle relaxants |
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What's a selective antagonist of GABA B?
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phaclofen
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List 8 roles of GABA in behavior
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aggression
feeding sexual behavior mood pain sensitivity locomotor activity cardiovascular regulation thermoregulation |
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What are two things that epileptics have that hint that decreased GABA function
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1. not as much GABA in CSF
2. less GAD when focusing (inconsistent though) |
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What has been shown to decrease convulsions? (and vice versa)
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increasing GABA
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How did Kindling model epilepsy?
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decreased GAD
decreased GABA conc alterations in GABA-R (binding and Cl- flux) |