Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Neuropharmacology > Chapter 8: Glutamate And GABA > Flashcards

Chapter 8: Glutamate And GABA Flashcards

(71 cards)

Start Studying
1
Q

Glutamine—>

A

Glutamate

Enzymes: glutaminase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Glutamine storage and release

A

VGLUT (vesicular glutamate transporter)- found only in cells that use Glu as NT

Either VGLUT1 or 2 are found in most neurons

      - VGLUT1- cortex and hippocampus
      - VGLUT2- subcortical structures

VGLUT3- inner hair cells of ear

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Glutamate inactivation

A

Excitatory amino acid transporters (EAATs)

EAAT1/2- expressed by astrocytes
- astrocytes play most important role in taking up Glu after release

EAAT3- found on postsynaptic cells

EAAT4- Purkinje cells in cerebellum

EAAT5- bipolar cells of retina

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Glutamate—>

A

Glutamine

Enzyme: glutamine synthetase
Location: astrocyte

*helps in metabolism and removal of ammonia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Glutamate is most abundant […] NT in the brain

A

Glutamate is most abundant excitatory NT in the brain

  • found in all neurons and glial cells
  • glutametergic neurons segregate Glu they use for transmission vs metabolism

Location:

  • Cortex
    - Pyramidal neurons- project to striatum, thalamus, limbic system structures, and brain stem
  • Cerebellum
    - Parallel fiber (GC’s) input to Purkinje neurons
  • Hippocampus
    - DG, CA1, CA3
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

The functional roles of Glu are important in neurotransmission, plasticity, and disease

A 
Fast excitatory neurotransmission
Learning and memory
      - neuronal plasticity
Neurological disorders
      - neurodegenerative disorders
      - cells death (excitotoxicity; apoptosis)

Possible involvement of Glu in drug addiction, schizophrenia, and other psychopathology

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Glu is an agonist of both […] and […] receptors

A

Glu is an agonist of both ionotropic and metabotropic receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

iGlu receptors

A

NMDA- Na+ and Ca2+ flow through channel
- Ca2+ activates 2nd- messenger system

non-NMDA- Na+ and K+ flows through receptor channels

   - AMPA
   - kainic acid (KA) - locomotor activity, coordination, and brain excitability
  • excitatory response
  • only has 4 subunits
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

mGlu receptors

A

Group I (mGlu1,5)- postsynaptic and excitatory responses via PIP2 system

Group II (mGlu2,3)- inhibit cAMP formation

Group III (mGlu4, 6 and 7)- inhibit cAMP formation
       - L-AP4 is selective agonist
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Non-NMDA Pharmacology

A

Agonists: AMPA and kainic acid
Antagonist: NBQX

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Non-NMDA Structure

A

GluA1-A4; GluA5-A7; KA1, KA2

4 subunits; dimer of dimers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Non-NMDA Physiology

A

Most AMPA/KA-R’s increases gNa+/gK+

GluA2- lacking AMPA receptors are Ca2+ permeable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

NMDA receptors are highly regulated

A

Ligand and voltage gated
Subunits:
GluN1 x2: Ser and Gly bind
GluN2 x2: Glu binds

Channels only open if:

  1. Glu is released into NMDA receptors
  2. Cell membrane is depolarized by stimulation of different excitatory receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

NMDA Co-agonists

A
  • Glutamate (NMDA)

- Glycine (D-serine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

NMDA receptor antagonists

A
  • Competitive: AP5 (APV)

- Non-competitive: PCP, MK-801, and Namenda, ketamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

NMDA Mg2+ block

A

Depolarization removes Mg2+ block

Highly Ca2+ permeable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Voltage-dependence of NR is due to […] in the […]

A

Voltage-dependence of NR is due to Mg2+ in the pore of the channel

Hyperpolarized Vm

    - Mg2+ blocks the channel
    - Non-conductive

Depolarized Vm

     - Mg2+ is expelled
     - Highly permeable to Ca2+
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

NMDA receptors are critical in some forms of […]

A

NMDA receptors are critical in some forms of LTP

  • Induction phase
  • Expression phase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Induction Phase of LTP

A
  • Depolarization
  • NMDA receptor activation
  • Ca2+ influx- activates protein kinases, including CAMKII
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Expression phase of LTP

A

Many kinases phosphorylate several targets involved in AMPA receptor trafficking

  • Receptor trafficking- NT receptors continuously moved into and out of cell membrane
  • CAMKII can stay activated even after Ca2+ return to baseline
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

[…] enhance cognitive function

A

AMPA receptor modulators enhance cognitive function

  • Nootropics
  • Ampakines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Ampakines

A
  • Positive allosteric modulators of AMPA receptors
  • Prevent deactivation and/or desensitization
  • Increase channel open time
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

The ampakine […] improves performance on the delayed match-to-sample task

A

The ampakine CX717 improves performance on the delayed match-to-sample task

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

The ampakine […] increases dendritic arborization and spine density in aged rats

A

The ampakine CX929 increases dendritic arborization and spine density in aged rats

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Excitotoxicity hypothesis
Prolonged neuronal depolarization leads to neuronal damage and/ or cell death
26
Three forms of cell death from strong activation of NMDA receptors
Necrosis- mode of cell death characterized by lysis of cell due to osmotic swelling Apoptosis (programmed cell death)- disruption of nucleus, DNA breakup, and cell death (cleared out by phagocytosis) Programmed necrosis- provoked by excitotoxic treatment of cells (necroptosis)
27
High [Glu]
- cell death by necrosis- characterized by lysis due to osmotic swelling - involves both NMDA and non-NMDA receptors
28
Lower [Glu]
Cell death by apoptosis (no lysis)
29
Amyotrophic Lateral Sclerosis (ALS)
Motor neuron disease caused by excitotoxicity - Treatment: Riluzole- reduces Glu release
30
Excitotoxic brain damage: domoic acid
Toxin made up of several species of marine algae
31
NMDA receptors are involved in 2 forms of cell death
Apoptosis | Programmed necrosis
32
Apoptosis
- capsase- dependent - cell shrinkage - DNA cleavage - Phagocytosis of debris
33
Programmed necrosis
- capable-independent - GluN2B- dependent - extrasynaptic location
34
[…] is a leading cause of death
- loss of blood supply to the brain - ischemic (occlusion) - hemorrhagic - O2 deprivation
35
O2 Deprivation (hypoxia)
Ischemic core - brain tissue that’s completely deprived of oxygen rapidly dies - ischemia- interruption of blood flow to brain due to excitotoxic brain damage Penumbra- area of partial deprivation surrounding the core
36
Loss of blood/ O2 initiated cell death
1. Loss of ATP 2. Pumps fail (Na+/K+ ATPase) - loss of ionic gradient - cell swelling/ rupture - membrane depolarization 3. Increased neuronal firing - excessive Glu release - NMDA-R activation - voltage-gated Ca2+ channel activation 4. Increased Ca2+ influx - Ca2+- activated protease and lipases - Free radical production 5. Cell death (programmed necrosis)
37
Treatment of stroke damage is largely unsuccessful
Restore blood supply Block Ca2+ influx Promote Glu clearance *Severe side-effects (eg. Psychosis)- too much time elapses between stroke and treatment
38
Restore blood supply
- Thrombolytics (TPA) | - Anticoagulants (heparin, warfarin)
39
Block Ca2+ influx
- NMDA receptor blockers - Glycine site - PCP site - voltage-gated Ca2+ channels blockers
40
Promote Glu clearance
Increase EAAT2 expression or function
41
Drugs that block GABA synthesis
Allyglycine, thiosemicarbazide, 3-mercaptopropanoic acid
42
GABA is found in […]
Cerebral cortex, hippocampus, substantia nigra - also cerebellum, striatum, globus pallidus, and olfactory bulbs - can be found in local interneurons and projection neurons (carry info longer distances) - only has job as NT and is manufactured by only GABAergic neurons
43
GABA is the most abundant […] NT in the brain
GABA is the most abundant inhibitory NT in the brain
44
CNS depressants
- Anxiolytics - Anesthetics - Sedatives - Anticonvulsants - Tiagabine (Gabitril) - Vigabatrin (Sabril)
45
Tiagabine (Gabritril)
Selective inhibitory of GAT-1 - increases extracellular GABA levels - increased GABA transmissions
46
Vigabratrin (Sabril)
Irreversible inhibitor of GABA-T | - prevents GABA metabolism and leads to buildup of GABA in brain
47
GABA precursor
Glutamate—> GABA Enzyme: Glutamic acid decarboxylase (GAD)
48
GABA packaging enzyme
Vesicular GABA transporter (VGAT) - same transporter used to load Gly into synaptic vesicles - sometimes referred to as VIAAT (vesicular inhibitory amino acid transporter)
49
GABA is coreleased with […]
GABA is coreleased with Gly, ACh, DA, and Glu - coexpression of multiple vesicular transporters must take place (ex VIAAT and VAChT) *Inhibitory neurons in CNS may release GABA only, Gly only, or both
50
GABA transporters
GAT-1 and GAT-2- found in both neurons and astrocytes GAT-3- astrocytes
51
GAT-1
Can be found in astrocytes and at nerve terminals of GABAergic neurons: important for GABA reuptake
52
GABA—> Glutamate
Enzyme: GABA amino-transferase (GABA-T) Location: astrocytes and neurons * final product: succinate * byproduct: glutamate * in astrocytes, further synthesized to glutamine (using glutamine synthetase) and transported back to nerve terminal via glutamine transporters)
53
GABAa ionotropic receptors are permeable to […] causing […]
GABAa ionotropic receptors are permeable to Cl- causing hyperpolarization
54
GABAa ionotropic receptor subunits
5 subunits 2 a, 2 B, 1 g Dominant type: (a1)2(B2)2(g2) Extrasynaptic receptors: (a4)2(Bx)2(d) OR (a6)2(Bx)2(d) - d binds neurosteroids and anesthetics - further away from release site on postsynaptic neuron
55
GABAa ionotropic receptor ligands
- muscimol (agonist) - Bucucculine (comp antagonist)- convulsant - Picrotoxin, PTZ (non- competitive antagonist)
56
GABA subunit binds on […] subunit
GABA subunit binds on B subunit
57
a5 subunit is expressed most in […]
a5 subunit is expressed most in hippocampus
58
Many CNS depressants are […] of GABAa receptors
Many CNS depressants are allosteric modulators of GABAa receptors
59
Positive allosteric modulators of GABAa
- Benzodiazepines - Barbituates - Ethanol, anesthetics, and neurosteroids
60
Benzodiazepines
Binding requires g2 subunit (a-g interface) Increases potency of GABA - Increases affinity of GABA for B-subunit - increases probability channel will open - increases Cl- influx - increases hyperpolarization * ex. Diazepam (Valium)- no effect on its own, but makes GABAergic response stronger
61
Behavioral effects of alpha subunits of benzodiazepines
a1- sedation - enhancement of tonic cellular inhibition - zolpidem (Ambien) a2/a3: anxiolytic - alprazolam (Xanax): most selective anxiolytic substance) a5- amnestic - found in hippocampus *low levels: reduce anxiety High levels: sedation
62
Barbituates
Habit forming, lethal in overdose (addiction potential) Binding site: - on B-subunit distinct from GABA/ agonist site - increases Cl- flux - increases channel open probability - increases duration of channel opening - can function in absence of agonist
63
Ethanol
Enhance GABAa receptor activity
64
Anesthetics
Includes voltage-gated ion channels and ligand-gated ion channels - propofol (Diprivan) - a5- amnestic
65
Neurosteroids
- Steroid hormones synthesized in brain that act locally on GABAa receptor - Binding site on d-subunit, converts GABA from partial agonist to full agonist (extrasynaptic receptor) Ex. Allopregnanolone (Zulresso) used in post-partum depression, allotetrahydrodeoxycorticosterone, and androstanediol
66
Negative allosteric modulators
Picrotoxin, pentylenetetrazol (PTZ) *convulsants
67
GABAb receptors are […]
GABAb receptors are metabotropic
68
Postsynaptic GABAb receptors
- open K+ channels | - inhibition of cAMP
69
Presynaptic GABAb receptors
- autoreceptors, heteroreceptors - inhibition of Ca2+ channels - inhibition of cAMP
70
GABAb agonist
Baclofen (Lioresal) - muscle relaxant and anti spastic agent
71
GABAb antagonist
Competitive antagonist: Saclofen and 2- hydroxysaclofen

Neuropharmacology (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions