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Flashcards in CNS 4 Deck (33)
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1
Q

what is glutamate?

A

most abundant amino acid

is intermediate in neuronal metabolism (precursor for GABA)

2
Q

what does glutamate act as?

A

major excitatory neurotransmitter in brain

3
Q

glutamate is synthesised in the nerve terminals from 2 sources

what are these?

A
  • from glucose via Krebs cycle

- from glutamine by enzyme glutamine
glutamine is synthesised by glia cells + taken up by neurones

4
Q

where is Glu stored?

A

vesicles + released by ca2+ dependent mechanism

5
Q

how is Glu removed?

A

from synapse by high affinity reuptake into nerve terminals + neighbouring glial cells

6
Q

the action of glutamate is not stopped by…

A

enzymatic breakdown

7
Q

what is the action of glutamate stopped by?

A

2 transport pumps (Na+/K+ coupled glutamate transporters)

8
Q

where are the Na+/K+ coupled glutamate transporters located?

A
  • first pumps in pre-sn

- second pumps in nearby glia cells

9
Q

glutamate taken up by …. is converted to glutamine

A

astroglial cells

10
Q

what is glutamine inactive in the sense?

A

it cannot activate glutamate receptors

it is released from glial cells into extracellular fluid

11
Q

what does glutamate act at?

A

3 different types of ionotropic receptors + at family at G protein coupled receptors

12
Q

describe the binding at ionotropic receptors?

A
  • NMDA receptors bind glutamate + NMDA
  • AMPA receptors bind glutamate, AMPA and quisqualic acid
  • kainate receptors bind glutamate + kainic acid
13
Q

what are metabotropic glutamate receptors (mGluRs)?

A

members of G protein coupled receptor (GPCR) superfamily

most abundant receptor gene family in human genome

14
Q

what do mGluRs mediate?

A

slow synaptic glutamate response by coupling to second messenger cascades + ion channels via heterotrimeric G proteins

15
Q

what are mGluRs linked to?

A

second messenger systems

lead to inc of intracellular ca2+ / dec of cAMP

16
Q

when mGluRs bind glutamate, what neurotransmitter do they create?

A

excitatory

17
Q

what members of the G protein coupled receptor family are mGluRs part of?

A

group C

18
Q

what do group I mGluRs couple to?

A

Gq/G11

  • activate phospholipase C
  • leads to hydrolysis of - phosphotinositides
  • generation of IP3 + DAG
19
Q

what do group II and III mGluRs couple to?

A

Gi/o

  • inhibit adenylyl cyclase
  • regulate ion channels + downstream signalling pathways
20
Q

what are glutamatergic neurones and NMDA receptors in the hippocampus important in?

A

creation of LTP (long term potentiation)

—> memory

21
Q

research studies show that the glutamate synapse is a potential target for wide range of neurological + psychiatric disorders.

give examples of these?

A
  • epilepsy
  • pain
  • anxiety
  • amnesia
22
Q

what is gamma-aminobutyric acid (GABA)?

A

amino acid with high conc in brain + spinal cord

23
Q

GABA is the most…

A

prevalent inhibitory neurotransmitter in CNS

24
Q

in the spinal cord, about half of inhibitory neurones use what instead?

A

glycine

25
Q

GABA does not penetrate through the blood brain barrier, therefore where is it synthesised?

A

in situ

26
Q

how is glutamate converted into GABA?

A

using L-glutamic acid decarboxylase (GAD)

27
Q

what does GAD require?

A

pyrodixal phosphate (active vitamin B6) as co factor

28
Q

where is GAD found?

A

in GABA-ergic neurones

present in nerve endings of brain as well as beta cells of pancreas

29
Q

what 2 forms of GAD are found in the brain?

A

GAD65, GAD67

30
Q

what are the 2 types of receptors for GABA in the mammalian CNS?

A
  • GABAA (ligand gated ion channels)

- GABAB (G protein coupled)

31
Q

give examples for GABAs normal + perturbed function?

A
  • cortical + thalamic - GABA neurones needed for inhibition of excitatory neurones
  • modulation of GABAa needed for treatment of anxiety disorders, insomnia + agitation
  • BZDs = helpful in treatment /prevention of seizures
  • BZDs also used in ethanol detoxification
32
Q

BZDs have a wide range of unwanted side effects

what are these?

A
  • hypotension
  • addition
  • impaired cognitive function
  • decreased libido / erection problems
33
Q

what are BZDs now replaced with?

A

SSRIs