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Neuropharmacology > Ketamine - glutamate neurotransmission > Flashcards

Ketamine - glutamate neurotransmission Flashcards

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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
how many possible different subunits in Kainate R
5
26
how many possible different subunits in NMDA R
7
27
GluA1 means
Glutamate AMPA receptor subunit 1
28
GluN1 means
Glutamate NMDA receptor subunit 1
29
Q/R site
determines Ca2+ permeability of GluA2
30
AMPA R permeability to Ca2+
nearly all AMPA R are Ca2+ impermeable | most contain GluA2 subunits
31
when are AMPA R permeable to Ca2+
in the absence of GluA2 subunits
32
competitive antagonist
NBQX
33
non-competitive antagonist
Telampanel
34
positive allosteric modulators
increase glutamate affinity | make desensitisation less effective
35
Ampakine
positive allosteric modulators of AMPA receptors
36
Ampakine effect
increases Glu signalling with same conc of Glu | enhances currents through AMPA R channels
37
day to day fundamental Glu signalling
via AMPA
38
Domoate
domoate is kainite receptor agonist | precusor for domoic acid --> environmental toxin
39
effects of domoic acid
crosses BBB | causes loss of short term memory, motor weakness, seizures, death
40
NMDA receptor activation
only under special circumstances
41
NMDA structure
heterotetramer 2 x GluN1 2 x GluN2
42
NMDA receptor properties
high Ca2+ permeability Mg2+ blocks the channel at resting potentials glycine necessary co-agonist
43
NMDA at -35mV
depolarising potential from AMPA R Mg2+ block removed from pore lots of Na can flow through
44
examples of drug binding sites on NMDA receptor
glutamate agonist/antagonist site glycine agonist/antagonist site allosteric modulators pore blockers
45
glycine agonist
D-serine | released by astrocytes
46
what does the affinity of glycine for GluN1 depend on
the type of GluN2
47
glycine antagonist function
prevents glycine co-activation of NMDA receptor
48
example of glycine antagonist
kynurenate
49
what are NMDA channel blockers
uncompetitive NMDA R antagonists
50
examples of uncompetitive NMDA R antagonists
ketamine | PCP
51
high affinity NMDA channel blocker
PCP (phencyclidine)
52
effects of ketamine
blocks NMDA R with low affinity induces sedation, immobility, analgesia damages bladder
53
phencyclidine
PCP high affinity uncompetitive antagonist of NMDA R blocks the channel
54
effects of PCP
hallucinogen | anaesthetic
55
difference between AMPA and NMDA EPSCs
NMDA EPSC is much longer-lasting | once Glu is bound to NMDA, takes longer to fall off
56
EPSP mediated by NMDA R
slow-rising, long-lasting excitatory | via Na+ and Ca2+
57
definition of synaptic plasticity
the ability to change the strength of synaptic connections and consolidate new pathways in the CNS
58
how do you induce LTP
``` high frequency (100Hz for 1 second) stimulation of hippocampal tissue slice specifically schaffer collateral pathway ```
59
examples of NMDA R-dependent hippocampal plasticity
LTP | LTD
60
effect of LTP
long-lasting increase in EPSP amplitude
61
stimulating LTD
1 Hz for 15 mins
62
effect of LTD
long lasting decrease in EPSP amplitude
63
pathophysiology of NMDA R
excitotoxicity epilepsy transmission of pain responses schizophrenia
64
excitotoxicity
over activation of NMDA too much glutamate signalling excessive entry of Ca2+ neuronal cell death
65
NMDA in epilepsy
NMDA Rs involved in development of seizures | anticonvulsant activity of NMDA R antagonists correlates with their affinity for NMDA R
66
NMDA in transmission of pain response
NMDA Rs are expressed on sensory neurons | maladaptive plasticity
67
NMDA and schizophrenia
hypofunction of NMDA R e.g. caused by PCP causes psychotic episodes
68
2 subclasses of glutamate transporter
EAAT (into cell) | VGLUT (cell cytoplasm --> vesicles)
69
3 kainate receptor agonists
kainate glutamate domoate

Neuropharmacology (14 decks)

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