Excitatory And Inhibitory AAs Flashcards Preview

Neurobiology > Excitatory And Inhibitory AAs > Flashcards

Flashcards in Excitatory And Inhibitory AAs Deck (56):
0

What are the two main excitatory NTs?

Glutamate and aspartate

1

What are the main inhibitory NTs:
a) in the brain
b) in the spinal cord

a) GABA
b) glycine

2

Glut, aspartate, GABA and glycine are NON-ESSENTIAL AAs. What does this mean?

They are synthesized in the body not required in diet

3

Describe the glycolysis/oxidative metabolism of glucose pathway of synthesising excitatory AAs (glut)

- Glucose converted to pyruvate in glycolysis
- Pyruvate is decarboxylated to form acetyl-CoA
- Acetyl-CoA enters the Krebs cycle
- a-ketoglutarate is produced in cycle, undergoes transamination by aminotransferases to form glutamate

4

What is the preferred pathway in synthesis of glutamate?

Glutaminase catalyses glutamine --> glutamate
(glutaminase undergoes product inhibition)

5

What are the 3 paths of glutamate breakdown?

* Glutamine synthetase - converts glutamate to Glutamine in glia

* reversal of transamination - glutamate -> a-ketoglutarate

* Glutamate dehydrogenase - glutamate -> a-ketoglutarate

6

How are EAAs stored?

In vesicles:
Highly specific transporter for L-glutamate
Proton antiporter system - actively moves H+ in, electrochem grad, transporter moves glut in and H+ out

7

Glutamate transporter concentrates glutamate in vesicles until it reaches a concentration of?

50mM

8

Describe release and uptake of EAAs (glutamate)

- vesicular release and uptake by presynaptic transporters

BUT also release by TRANSPORTER REVERSAL

Transporters have high affinity and low specificity

9

How many glutamate transporter subtypes are there?

5

10

Where are glutamate transporters EAAT1-5 each found?

EAAT1 - neurones an astroglia (esp Bergmann glia, cortex, hippocampus and cerebellum)
EAAT2 - astroglia
EAAT3 - neurones
EAAT4 - Cerebellar purkinje cells
EAAT5 - retina

11

Which metabotropic glutamate receptor subtypes are in GROUP I? What do they stimulate?
What compounds are they activated by?

mGluR1 + mGluR5

Gq - stimulate PLC -> IP3 (Ca release)

Activated by trans-ACPD and quisqualate

12

Which metabotropic glutamate receptor subtypes are in GROUP II? What do they stimulate?
What compounds are they activated by?

mGluR2 + mGluR3

Gi - inhibit adenylyl cyc

Actuated by trans-ACPD and quisqualate

13

Which metabotropic glutamate receptor subtypes are in GROUP III? What do they stimulate?
What compounds are they activated by?

mGluR4, 6, 7, 8

Gi - inhibit adenylyl cyc

Activated by L-AP4 and L-SOP (no effect w trans-ACPD or quisqualate)

14

Which group of mGluRs act as autoreceptors?

Group III

15

What ions do AMPA, kainate and NMDA allow?

AMPA - Na, K (and some allow Ca)

Kainate - Na, K

NMDA - Na, K, Ca

16

Quisqualate is an agonist of which IONOTROPIC receptors?

AMPA and kainate

17

What is an agonist of NMDA receptor?

Aspartate

18

CNQX is an antagonist of which glutamate receptors?

AMPA

Kainate

19

AP5 is an antagonist of which type of glutamate receptor?

NMDA

20

How does a conditioning train result in long term potentiation?

= rapid stimulation
Changes efficiency of synapse, makes it stronger
Results in larger responses
Responsible for synaptic plasticity

Train -> sustained depolarization, NMDA block removed
Metabotropic glut receptors activated
AMPA phosphorylation, increased AMPA activity

21

How do EEA IONOTROPIC receptors cause stroke, Alzheimer's and amyotrophic lateral sclerosis?

Sustained activation of AMPA, kainate and esp NMDA receptors
Leads to neuronal cell death due to Ca overload
=> neurodegeneration

22

What can provoke overstimulation of EAA receptors and consequently neurodegeneration?

Clue - restriction of blood supply

Ischemia

23

What's the main inhibitory transmitter in:
a) the brain?

b) the spinal cord?

a) GABA

b) glycine

24

What is GABA synthesized from?

What enzyme catalyses it's synthesis?

Where is this enzyme mostly found, what co-factor does it require, and what inhibits it?

Glutamate

Glutamate decarboxylase

Axon terminals of GABAergic neurones.
Pyridoxal phosphate derived from vitB
Inhibited by allylglycine.

25

How is GABA broken down?

Converted in succinic semialdehyde by GABA aminotransferase

Succinic semialdehyde converted to succinate by SSADH (succinic semialdehyde dehydrogenase)

(Succinate = intermediate in Krebs)

26

Where is GABA aminotransferase found?

What inhibits it? What are it's inhibitors used for?

Mostly in mitochondria (in neurones and Astrocytes)

Inhibitors: aminooxyacetic acid and vigabatrin
Vigabatrin used to treat epilepsy

27

Which GABA receptors are IONOTROPIC?

A + C

B is metabotropic

28

Where is GABAc mainly located?

In retina

29

Why is there huge diversity in GABAa receptors?

6 classes if subunit: a, B, y, d, E, p

19 different polypeptides

30

What domain of GABAa is thought to line the pore?

What controls permeation?

M2

Charged rings

31

What forms the GABA binding site on GABAa receptor?

Cys (cystine) loop

32

GABA has 5 distinct binding sites for what molecules?

What do agonists of these sites do? (In brackets)

1) GABA
2) benzodiazepine
3) barbiturates (depressants)
4) steroids (anaesthetics)
5) picrotoxin (convulsants)

33

Why do benzodiazepines and barbiturates decrease anxiety?

Potentiation GABA

34

What 3 agonists of GABAa?

Muscimol, THIP, isoguvacine

35

What is a competitive antagonist of GABAa?

Bicuculline

36

What are non-competitor antagonists of GABAa?

Metrazol (phentylenetrazol)
and
Picrotoxin

(Both bind to picrotoxin site)

37

How do benzodiazepines and barbiturates affect channel openings of GABAa?

Benzodiazepines: increase FREQUENCY of openings

Barbiturates: increase DURATION of openings

38

What is the most common subunit composition if GABAa (40%)?

Where is this isoform located and what are it's properties at these locations?

a1B2y2

Most brain areas, hippocampus - common coassembly

Cortical interneurones - BZ type I

Cerebellar purkinje cells - Zn insensitive

39

What subunit is required for GABAa to respond to benzodiazepines?

Y

40

How does GABAb bring about synaptic inhibition of NT release?

Coupled to Gi, inhibits adenyl cyclase

Stimulates PLA2

Activates VG K+ channels
Inhibits Ca channels
=> hyperpolarisation, no NT release

41

What are agonists of GABAb? What are they used for?

Baclofen, saclofen

Muscle relaxants, anti spastic agents

42

Phaclofen-2-hydroxysaclofen does what to which GABA receptor?

Antagonist of GABAb

43

What five places are glycine receptors found?

Spinal cord grey matter
Mindbrain (lower levels)
Medulla
Thalamus
Hypothalamus

NB: absent from higher brain levels

44

What is glycine synthesised from? Using what enzyme?

Serine

Serine hydroxymethyltransferase

45

How is glycine stored?

In vesicles

Vesicular transporter hasn't been found, most likely uses GABA transporter

46

How is glycine taken up from synapse?

Na dependent transporters
Specific (GLYT1, GLYT2)

47

How many subunits make up a glycine receptor?

What classes of subunit? What type of protein are these subunits?

5

a (a1,a2, a3) and B
Glycoproteins

48

How many transmembrane domains make up each subunit if GlyR?

4

49

What subunit composition of glycine receptor is found in adults? And in fetus?

Adult: 3a1/2B

Fetus: 5a2 (homomer)

50

What other protein is associated with glycine receptor? Why is it's role?

Gephrin
Cytoplasmic protein

Binds B subunit to cytoskeleton
Responsible for GlyR clustering at inhibitory synapse

51

What is an allosteric modulator of glycine receptor?

Zinc

52

Which of the following: B-alanine, cyanotriphenylborate, taurine, strychnine

are a) agonists b) antagonists and c) channel blockers of glycine receptor?

a) B-alanine, taurine

b) strychnine

c) cyanotriphenylborate

53

How does tetanus toxin affect glycine receptor?

Causes Glycine release

(=> over activation of muscles)

54

What role do glycine receptors have in whole organism?

Reflex responses- reciprocal and recurrent inhibition

Sensory processing

Voluntary muscle control

55

Hyperekplexia (exaggerated reflexes) is caused by mutation of glycine receptors, decreases glycine signalling.

How is it treated?

With benzodiazepines (increase GABA activity in SC)