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Neuropharmacology > Ketamine - glutamate neurotransmission > Flashcards

Ketamine - glutamate neurotransmission Flashcards

1
Q

fast transmission utilise which type of receptors

A

ligand gated ion channel

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2
Q

behaviours that use fast transmission

A

sight
reflexes
audition

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3
Q

fast neurotransmitter examples

A

glutamate
GABA
Glycine

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4
Q

glutamate

A

= fast, excitatory

makes up 90% of synaptic communications in the brain

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5
Q

history and first evidence of glutamate

A

Hayashi 1954

David curtis and watkins 1959

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6
Q

Hyashi 1954

A

induced seizures in dogs and monkeys

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7
Q

David Curtis
Watkins
1959

A

used cats and found first real evidence that Glu was excitatory
used microelectrophoretic techniques

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8
Q

dendritic spines

A

narrow neck and wider head with PSD

where the synapses are made between dendrite and post synaptic membrane

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9
Q

PSD

A

post synaptic density

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10
Q

5 core components of neurotransmitter system

A 
1 - molecules to synthesise NT
2 - transporters for NT entry into cells
3 - transporters for NT entry into vesicles
4 - receptors activated by NT
5 - molecules to terminate NT action
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11
Q

glutamate biosynthesis

A

e.g. glutamine precursor + H2O –> Glu + NH3

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12
Q

is glutamate an essential amino acid

A

no
non essential
not necessary in diet

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13
Q

transporters to get glutamate into cells

A

EAAT 1-5

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14
Q

main transporter to get glutamate into cells

A

EAAT2

mediates 90% of Glu uptake into cells

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15
Q

transporters to get glutamate into vesicles

A

VGLUT 1-3

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16
Q

receptors activated by glutamate

A

AMPA
NMDA
Kainate
mGluRs

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17
Q

termination of glutamate activity

A

diffusion

uptake into cells via EAAT mediators

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18
Q

3 components of tripartite synapse

A

neuronal terminal
post-synaptic membrnae
astrocyte

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19
Q

why are astrocytes important

A

its important not to have too much Glu floating around to prevent over activation

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20
Q

glutaminase

A

enzyme

converts glutamine into glutamate

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21
Q

ionotropic Glu receptor features

A

ligand gated ion channel

rapid tranmission

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22
Q

metabotropic Glu receptor features

A

GPCR
signal via 2nd messenger cascades
7TM subunits

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23
Q

3 families of ionotropic Glu R

A

AMPA
Kainate
NMDA

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24
Q

how many possible different subunits in AMPA R

A

4

tetrameric

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25
Q

how many possible different subunits in Kainate R

A

5

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26
Q

how many possible different subunits in NMDA R

A

7

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27
Q

GluA1 means

A

Glutamate AMPA receptor subunit 1

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28
Q

GluN1 means

A

Glutamate NMDA receptor subunit 1

29
Q

Q/R site

A

determines Ca2+ permeability of GluA2

30
Q

AMPA R permeability to Ca2+

A

nearly all AMPA R are Ca2+ impermeable

most contain GluA2 subunits

31
Q

when are AMPA R permeable to Ca2+

A

in the absence of GluA2 subunits

32
Q

competitive antagonist

A

NBQX

33
Q

non-competitive antagonist

A

Telampanel

34
Q

positive allosteric modulators

A

increase glutamate affinity

make desensitisation less effective

35
Q

Ampakine

A

positive allosteric modulators of AMPA receptors

36
Q

Ampakine effect

A

increases Glu signalling with same conc of Glu

enhances currents through AMPA R channels

37
Q

day to day fundamental Glu signalling

A

via AMPA

38
Q

Domoate

A

domoate is kainite receptor agonist

precusor for domoic acid –> environmental toxin

39
Q

effects of domoic acid

A

crosses BBB

causes loss of short term memory, motor weakness, seizures, death

40
Q

NMDA receptor activation

A

only under special circumstances

41
Q

NMDA structure

A

heterotetramer
2 x GluN1
2 x GluN2

42
Q

NMDA receptor properties

A

high Ca2+ permeability
Mg2+ blocks the channel at resting potentials
glycine necessary co-agonist

43
Q

NMDA at -35mV

A

depolarising potential from AMPA R
Mg2+ block removed from pore
lots of Na can flow through

44
Q

examples of drug binding sites on NMDA receptor

A

glutamate agonist/antagonist site
glycine agonist/antagonist site
allosteric modulators
pore blockers

45
Q

glycine agonist

A

D-serine

released by astrocytes

46
Q

what does the affinity of glycine for GluN1 depend on

A

the type of GluN2

47
Q

glycine antagonist function

A

prevents glycine co-activation of NMDA receptor

48
Q

example of glycine antagonist

A

kynurenate

49
Q

what are NMDA channel blockers

A

uncompetitive NMDA R antagonists

50
Q

examples of uncompetitive NMDA R antagonists

A

ketamine

PCP

51
Q

high affinity NMDA channel blocker

A

PCP (phencyclidine)

52
Q

effects of ketamine

A

blocks NMDA R with low affinity
induces sedation, immobility, analgesia
damages bladder

53
Q

phencyclidine

A

PCP
high affinity uncompetitive antagonist of NMDA R
blocks the channel

54
Q

effects of PCP

A

hallucinogen

anaesthetic

55
Q

difference between AMPA and NMDA EPSCs

A

NMDA EPSC is much longer-lasting

once Glu is bound to NMDA, takes longer to fall off

56
Q

EPSP mediated by NMDA R

A

slow-rising, long-lasting excitatory

via Na+ and Ca2+

57
Q

definition of synaptic plasticity

A

the ability to change the strength of synaptic connections and consolidate new pathways in the CNS

58
Q

how do you induce LTP

A 
high frequency (100Hz for 1 second) stimulation of hippocampal tissue slice 
specifically schaffer collateral pathway
59
Q

examples of NMDA R-dependent hippocampal plasticity

A

LTP

LTD

60
Q

effect of LTP

A

long-lasting increase in EPSP amplitude

61
Q

stimulating LTD

A

1 Hz for 15 mins

62
Q

effect of LTD

A

long lasting decrease in EPSP amplitude

63
Q

pathophysiology of NMDA R

A

excitotoxicity
epilepsy
transmission of pain responses
schizophrenia

64
Q

excitotoxicity

A

over activation of NMDA
too much glutamate signalling
excessive entry of Ca2+
neuronal cell death

65
Q

NMDA in epilepsy

A

NMDA Rs involved in development of seizures

anticonvulsant activity of NMDA R antagonists correlates with their affinity for NMDA R

66
Q

NMDA in transmission of pain response

A

NMDA Rs are expressed on sensory neurons

maladaptive plasticity

67
Q

NMDA and schizophrenia

A

hypofunction of NMDA R
e.g. caused by PCP
causes psychotic episodes

68
Q

2 subclasses of glutamate transporter

A

EAAT (into cell)

VGLUT (cell cytoplasm –> vesicles)

69
Q

3 kainate receptor agonists

A

kainate
glutamate
domoate

Neuropharmacology (14 decks)

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