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Neuropharmacology & Neuroscience > Excitatory and Inhibitory Amino Acids > Flashcards

Excitatory and Inhibitory Amino Acids Flashcards

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
Q

Which technique was used to discover NMDA receptors?

A

Patch receptor testing

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26
Q

Which co-factor is required for glutamate to be able to bind to NMDA?

A

Glycine

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27
Q

Name 3 other typical NMDA antagonists

A

Phencyclidine, ketamine and MK801 ion channel blockers

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28
Q

What are metabotropic glutamate receptors linked to?

A

They are GPCR linked. They are either linked to Gq or Gi

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29
Q

What happens when Gq is activated?

A

It activates PLC, which activates DAG and IP3. This in turn increases intracellular calcium

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30
Q

What happens when Gi is activated?

A

It inhibits Adenylyl cyclase, which means ATP is not converted to cAMP. This means cAMP is not able to activate PKC.

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31
Q

What are the metabotropic glutamate receptor types?

A

Glu R 1, 2, 3, 4, 5, 6, 7 and 8

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32
Q

Which of the metabotropic Glu R are in group 1?

A

Glu R 1 and 5

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33
Q

Which of the metabotropic Glu R are in group 2?

A

Glu R 2 and 3

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34
Q

Which of the metabotropic Glu R are in group 3?

A

Glu R 4, 6 and 8

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35
Q

Which G protein are group 1 Glu R linked to?

A

Gq (PLC)

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36
Q

Which G protein are group 2 Glu R linked to?

A

Gi (AC)

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36
Q

Which G protein are group 3 Glu R linked to?

A

Gi (AC)

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37
Q

What is the difference between groups 2 and 3 Glu R?

A

Whilst they have the same GPCR and second messengers, they are pharmacologically distinct

38
Q

Name an agonist for groups 1 and 2

A

ACPD

39
Q

What does MCPG do to metabotropic Glu R?

A

Non selectively antagonises them

40
Q

What is IAHP?

A

Inhibitory After HyperPolarisation. This mechanism induces the absolute refractory period.

41
Q

What is an M-current?

A

The current is produced as a result of the M-class K+ channel. These channels cause an increase in the action potential threshold

42
Q

What happens as a result of M-currents?

A

A slow EPSP is generated

43
Q

What are the electrophysiological effects of metabotropic Glu R?

A

IAHP, M-currents and Voltage-dependent Ca2+ channels are blocked

44
Q

What is the function of metabotropic Glu R?

A

1) They act as a neuromodulator, akin to ACh but in the CNS
2) Slow EPSP
3) Synaptic plasticity

45
Q

What is the function of AMPA receptors?

A

They mediate fast EPSP in the CNS

46
Q

What is the function of Kainate receptors?

A

They modulate the transmission of fast EPSP pre and postsynaptically

47
Q

Which processes are NMDA receptors involved with?

A

Learning, memory and developmental plasticity

48
Q

Which pathologies are associated with metabotropic Glu R?

A

Schizophrenia, Fragile X and Parkinsons

49
Q

Which pathologies are associated with AMPA receptors?

A

Epilepsy

50
Q

Which pathologies are associated with Kainate receptors?

A

Schizophrenia, depression and autism

51
Q

Which pathologies are associated with NMDA receptors?

A

Epilepsy and excitotoxicity

52
Q

What is the primary inhibitory amino acid?

A

GABA

53
Q

Which enzyme synthesises GABA and what is GABAs precursor?

A

Glutamate is converted to GABA by glutamic acid decarboxylase

54
Q

Which enzyme breaks down GABA?

A

GABA transaminase

55
Q

How is GABA uptaken?

A

Presynaptically

56
Q

What are the types of GABA receptors?

A

GABAa and GABAb
GABAa is more common

57
Q

Name two techniques used to locate GABA receptors

A

GAD staining and radioligand binding

58
Q

What is the primary difference between GABAa and GABAb?

A

GABAa is ionotropic whereas GABAb is metabotropic

59
Q

What are some key characteristics of GABAa?

A

It is permeable to Cl-, produces fast IPSP and has a reversal potential of -75mV

60
Q

What is the primary synthetic agonist for GABAa receptors?

A

Muscimol

61
Q

What is the primary antagonist for GABAa receptors

A

Bisculline (GABAzine)

62
Q

How many subunits can form GABAa?

A

16, although it is a pentamer so only 5 are involved at any one time

63
Q

Which toxin can block the GABAa channel?

A

Picrotoxin

64
Q

What effect do benzodiazepines have on GABAa receptors?

A

They increase the conductance of the channels

65
Q

What effect do barbituates have on GABAa receptors?

A

Increase the time the channel is open for

66
Q

What is the structure of GABAb receptors known as?

A

It is heterodimeric

67
Q

What is the primary synthetic agonist for GABAb receptors?

A

Baclofen

67
Q

What is the primary synthetic antagonist for GABAb receptors?

A

Phaclofen

68
Q

Which ion are GABAb permeable to?

A

K+

69
Q

What occurs as a response to GABAb permeability to K+?

A

It has a reversal potential of +90mV and generates slow IPSPs

70
Q

GABAb receptor activation can result in a direct blockage of which other receptor?

A

Voltage-dependent Ca2+ channels

71
Q

How does inhibition of voltage-dependent Ca2+ channels result in a slow IPSP?

A

It inhibits NT release

72
Q

Which pathology are GABA receptors associated with?

A

Epilepsy

73
Q

Why are GABA receptors linked to epilepsy?

A

Dysfunction of the inhibition of neural discharge is thought to contribute to seizure activity

74
Q

Progabide is an AED that uses this principle, what is its mechanism of action?

A

It increases formation of GABA

75
Q

Valproic acid is an AED that uses this principle, what is its mechanism of action?

A

It inhibits GABA transaminase (the breakdown of GABA)

76
Q

Barbiturates are used as AEDs, what is their broad mechanism of action?

A

They increase the potentiation of GABA responses

77
Q

Which drug class has a tranquilising effect mediated by GABA receptors?

A

Benzodiazepines

78
Q

Which drug class has anaesthetic effects mediated by GABA receptors?

A

Barbiturates

78
Q

Which pathology is associated with a loss of GABA receptors and function?

A

Alcohol dependency

79
Q

What is another important inhibitory amino acid?

A

Glycine

80
Q

Where are glycine receptors most commonly found?

A

The brain stem and spinal cord

81
Q

What are glycine receptors permeable to?

A

Cl-

82
Q

As a result of GlyR being permeable to Cl-, what is the reversal potential of the receptor?

A

-75mV

83
Q

Bearing in mind that GlyR are ionotropic, what do they generate?

A

Fast IPSP

84
Q

What are the primary agonists of GlyR?

A

Glycine and alanine. Although alanine can agonise the receptor, it is not found to actually act as a neurotransmitter

85
Q

What is the primary antagonist of GlyR?

A

Strychnine

86
Q

GlyR form which structure with which subunits?

A

It forms a pentamer with α-1, α-2 and β subunits

87
Q

Which notable cell population is glycinergic?

A

Renshaw cells

88
Q

Where are Renshaw neurons found and what is their function?

A

They are found in the spinal cord and car as modulators to motorneurons

89
Q

Faulty glycinergic receptors are found commonly in which conditions?

A

Spasticity

90
Q

Which drug can be used to treat spasticity?

A

Baclofen

Neuropharmacology & Neuroscience (10 decks)

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