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Neuropharmacology & Neuroscience > Excitatory and Inhibitory Amino Acids > Flashcards

Excitatory and Inhibitory Amino Acids Flashcards

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1
Q

What is the primary excitatory amino acid?

A

L-glutamate

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2
Q

What does l-glutamate act as?

A

A neurotransmitter

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3
Q

Which enzymes form L-glutamate?

A

Glutaminase or GABA transaminase

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4
Q

Which enzymes form L-glutamate?

A

Glutaminase or GABA transaminase

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5
Q

How is glutamate inactivated?

A

By reuptake

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6
Q

What are the key features of AMPA receptors?

A

They are ionotropic monovalent cation channels

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7
Q

What do activated AMPA receptors generate?

A

EPSP, largely by Na+ influx

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8
Q

What is the synthetic agonist of AMPA receptors

A

AMPA

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9
Q

What is the synthetic antagonist of AMPA receptors?

A

NBQX

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10
Q

What are the subunits of AMPA receptors, and what do they form?

A

Glu A 1, 2, 3 and 4
A tetramer

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11
Q

How many transmembrane domains do AMPA receptors have?

A

Three, with another domain that is partially transmembrane

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12
Q

What are AMPA receptors similar to?

A

nAChr but in the CNS

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13
Q

What are the subunits of Kainate receptors?

A

Glu K 1, 2, 3, 4 and 5

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14
Q

What do the kainate subunits form?

A

They form a tetramer; the subunits present in any one kainate receptor change over time

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15
Q

What are the 3 key features of kainate receptors?

A

1) They are rapidly desensitising
2) They act differently post and pre synaptically
3) They are involved in neuronal maturation

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16
Q

What are some key features of NMDA receptors?

A

They are ionotropic Na+, K+ and Ca2+ channels.
They have a reversal potential of roughly 0mV

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17
Q

What do NMDA generate?

A

relatively fast EPSP

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18
Q

What is the synthetic agonist of NMDA receptors?

A

NMDA

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19
Q

What is the antagonist of NMDA receptors?

A

AP5

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20
Q

What is the antagonist of NMDA receptors?

A

AP5

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21
Q

What are the subunits of NMDA receptors?

A

Glu N1 and Glu N2 A, B, C and D

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22
Q

What structure do NMDA receptors form?

A

A tetramer- the composition of subunits changes over time

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23
Q

What does Mg2+ do to NMDA receptors?

A

It modulates them by causing a voltage-dependent block

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24
Q

When does Mg2+ cause the NMDA block?

A

When the electrochemical gradient is pulling positive ions into the cell

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25
Which technique was used to discover NMDA receptors?
Patch receptor testing
26
Which co-factor is required for glutamate to be able to bind to NMDA?
Glycine
27
Name 3 other typical NMDA antagonists
Phencyclidine, ketamine and MK801 ion channel blockers
28
What are metabotropic glutamate receptors linked to?
They are GPCR linked. They are either linked to Gq or Gi
29
What happens when Gq is activated?
It activates PLC, which activates DAG and IP3. This in turn increases intracellular calcium
30
What happens when Gi is activated?
It inhibits Adenylyl cyclase, which means ATP is not converted to cAMP. This means cAMP is not able to activate PKC.
31
What are the metabotropic glutamate receptor types?
Glu R 1, 2, 3, 4, 5, 6, 7 and 8
32
Which of the metabotropic Glu R are in group 1?
Glu R 1 and 5
33
Which of the metabotropic Glu R are in group 2?
Glu R 2 and 3
34
Which of the metabotropic Glu R are in group 3?
Glu R 4, 6 and 8
35
Which G protein are group 1 Glu R linked to?
Gq (PLC)
36
Which G protein are group 2 Glu R linked to?
Gi (AC)
36
Which G protein are group 3 Glu R linked to?
Gi (AC)
37
What is the difference between groups 2 and 3 Glu R?
Whilst they have the same GPCR and second messengers, they are pharmacologically distinct
38
Name an agonist for groups 1 and 2
ACPD
39
What does MCPG do to metabotropic Glu R?
Non selectively antagonises them
40
What is IAHP?
Inhibitory After HyperPolarisation. This mechanism induces the absolute refractory period.
41
What is an M-current?
The current is produced as a result of the M-class K+ channel. These channels cause an increase in the action potential threshold
42
What happens as a result of M-currents?
A slow EPSP is generated
43
What are the electrophysiological effects of metabotropic Glu R?
IAHP, M-currents and Voltage-dependent Ca2+ channels are blocked
44
What is the function of metabotropic Glu R?
1) They act as a neuromodulator, akin to ACh but in the CNS 2) Slow EPSP 3) Synaptic plasticity
45
What is the function of AMPA receptors?
They mediate fast EPSP in the CNS
46
What is the function of Kainate receptors?
They modulate the transmission of fast EPSP pre and postsynaptically
47
Which processes are NMDA receptors involved with?
Learning, memory and developmental plasticity
48
Which pathologies are associated with metabotropic Glu R?
Schizophrenia, Fragile X and Parkinsons
49
Which pathologies are associated with AMPA receptors?
Epilepsy
50
Which pathologies are associated with Kainate receptors?
Schizophrenia, depression and autism
51
Which pathologies are associated with NMDA receptors?
Epilepsy and excitotoxicity
52
What is the primary inhibitory amino acid?
GABA
53
Which enzyme synthesises GABA and what is GABAs precursor?
Glutamate is converted to GABA by glutamic acid decarboxylase
54
Which enzyme breaks down GABA?
GABA transaminase
55
How is GABA uptaken?
Presynaptically
56
What are the types of GABA receptors?
GABAa and GABAb GABAa is more common
57
Name two techniques used to locate GABA receptors
GAD staining and radioligand binding
58
What is the primary difference between GABAa and GABAb?
GABAa is ionotropic whereas GABAb is metabotropic
59
What are some key characteristics of GABAa?
It is permeable to Cl-, produces fast IPSP and has a reversal potential of -75mV
60
What is the primary synthetic agonist for GABAa receptors?
Muscimol
61
What is the primary antagonist for GABAa receptors
Bisculline (GABAzine)
62
How many subunits can form GABAa?
16, although it is a pentamer so only 5 are involved at any one time
63
Which toxin can block the GABAa channel?
Picrotoxin
64
What effect do benzodiazepines have on GABAa receptors?
They increase the conductance of the channels
65
What effect do barbituates have on GABAa receptors?
Increase the time the channel is open for
66
What is the structure of GABAb receptors known as?
It is heterodimeric
67
What is the primary synthetic agonist for GABAb receptors?
Baclofen
67
What is the primary synthetic antagonist for GABAb receptors?
Phaclofen
68
Which ion are GABAb permeable to?
K+
69
What occurs as a response to GABAb permeability to K+?
It has a reversal potential of +90mV and generates slow IPSPs
70
GABAb receptor activation can result in a direct blockage of which other receptor?
Voltage-dependent Ca2+ channels
71
How does inhibition of voltage-dependent Ca2+ channels result in a slow IPSP?
It inhibits NT release
72
Which pathology are GABA receptors associated with?
Epilepsy
73
Why are GABA receptors linked to epilepsy?
Dysfunction of the inhibition of neural discharge is thought to contribute to seizure activity
74
Progabide is an AED that uses this principle, what is its mechanism of action?
It increases formation of GABA
75
Valproic acid is an AED that uses this principle, what is its mechanism of action?
It inhibits GABA transaminase (the breakdown of GABA)
76
Barbiturates are used as AEDs, what is their broad mechanism of action?
They increase the potentiation of GABA responses
77
Which drug class has a tranquilising effect mediated by GABA receptors?
Benzodiazepines
78
Which drug class has anaesthetic effects mediated by GABA receptors?
Barbiturates
78
Which pathology is associated with a loss of GABA receptors and function?
Alcohol dependency
79
What is another important inhibitory amino acid?
Glycine
80
Where are glycine receptors most commonly found?
The brain stem and spinal cord
81
What are glycine receptors permeable to?
Cl-
82
As a result of GlyR being permeable to Cl-, what is the reversal potential of the receptor?
-75mV
83
Bearing in mind that GlyR are ionotropic, what do they generate?
Fast IPSP
84
What are the primary agonists of GlyR?
Glycine and alanine. Although alanine can agonise the receptor, it is not found to actually act as a neurotransmitter
85
What is the primary antagonist of GlyR?
Strychnine
86
GlyR form which structure with which subunits?
It forms a pentamer with α-1, α-2 and β subunits
87
Which notable cell population is glycinergic?
Renshaw cells
88
Where are Renshaw neurons found and what is their function?
They are found in the spinal cord and car as modulators to motorneurons
89
Faulty glycinergic receptors are found commonly in which conditions?
Spasticity
90
Which drug can be used to treat spasticity?
Baclofen

Neuropharmacology & Neuroscience (10 decks)

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