Excitatory transmission Flashcards

1
Q

What are the 3 subtypes of ionotropic glutamate (D) receptors?

A
  • AMPA
  • KAINATE
  • NMDA
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2
Q

what neurotransmitters is AMPA receptor sensitive to?
- Kainic acid
- AMPA
- NMDA
- glutamic acid

A
  • glutamate, AMPA
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3
Q

what nt´s is Kainate receptor sensitive to?

A
  • Glutamic acid
  • kainic acid
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4
Q

what nt´s is NMDA receptor sensitive to?

A
  • glutamic acid (response is very weak though)
  • NMDA (also not a very sharp response)
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5
Q

which of the aforementioned glutamate receptors is blocked by Mg at -60 mV (voltage dependent block) ?

A
  • NMDA receptor
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6
Q

conditions for NMDA receptor opening and generation of inward current

A
  • binding of glutamate/NMDA and glycine co-activator
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7
Q

what are the (two) NMDA receptor co-agonists?

A
  • Glycine
  • D-serine
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8
Q

What are the (two) NMDA subunits and what do they bind?

A
  • GluN1 binds co-agonist (glycine/D-serine )
  • GluN2 binds glutamate
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9
Q

in terms of fast/slow EPSC, what type of EPSC does NMDA mediate?
- provide NMDA antagonist that inhibits slow EPSC

A
  • slow EPSC
  • APV NMDA receptor antagonist (only affects slow EPSC)
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10
Q

in terms of fast/slow EPSC, what type of EPSC does AMPA receptor mediate?
- provide name AMPA antagonist

A
  • mediates fast EPSC component
  • CNQX antagonist (only affects fast EPSC)
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11
Q

Glycine is a co-activator which is required for NMDA channel opening.

assuming all receptors present, what happens to the current if there is only glutamate (no co-activator) present?

A

Glutamate can still induce current due to AMPA receptor activation

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12
Q

What conditions can lead to overcoming of Mg blockage of NMDA receptors?

A
  • high frequency presynaptic glutaminergic nerve firing
  • multiple glutaminergic inputs

both lead to sufficient depolarization to cause Mg unblocking

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13
Q

What is a characteristic of NMDA receptor-mediated depolarization (after Mg blocking)

A
  • slow, prolonged synaptic depolarization
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14
Q

what are some channel blockers of NMDA receptor?

A
  • PCP
  • ketamine
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15
Q

explain Temporal summation of excitatory postsynaptic potentials mediated by ionotropic glutamate receptors

A
  • from a single presynaptic nerve fiber firing APs in quick succession, which summate
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16
Q

what is the structure subunit assembly of all ionotropic glutamate receptors?

A
  • tetrameric
17
Q

the GluA2 subunit of AMPA receptor has what characteristics?

A
  • containsQ/R site responsible for Ca permeability/impermeability
  • also determines whether AMPA is sucsceptible (Q present) to receptor blockage by polyamines
18
Q

amino acid located in AMPA ion conducting pore that confers Ca permeability (present in non-edited GluA2 subunit)?

A
  • Glutamine (Q)
19
Q

Amino acid in ion conducting pore that confers ion IMpermeability?

A

Arginine (R)

20
Q

in adults, which version of GluA2 is most common (95%)?
- GluAK
- GluA2
-GluAR
- GluAQ

A

-GluAR (edited version)

21
Q

what occurs in gluA2 Q to R editing?

A

adenosinne deamination to inosine– read as guanisine

22
Q

what spermine and what is its relation to AMPA receptors

A
  • intracellular AMPAr antagonist that blocks outward cation movement
  • acts on AMPArs lacking GluA2/non-edited GluA2 AMPArs (GluA2Q)
23
Q

why are is the expression of Ca permeable AMPARs important in early development?

A
  • mediates synaptic plasticity and long term potentiation
24
Q

evidence for S1-S2 glutamate receptor subunit being the ligand binding domain?

A
  • shows sequence homology to bacterial AA binding proteins
  • ligand binding stabilizes the closed state
25
Q

would S1/S2 domain swapping between GluA3 (AMPAR) and GluK2 (kainateR) affect agonist pharmacology ?

A

yes

26
Q

what is the NMDA receptor equivalent of the AMPAR Q/R site at M2 subunit (hint: site of Mg2 block) ?

A
  • asparagine residue
27
Q

At a membrane potential of -60 mV

  • in what direction is the net flow of current (and what ions are the drivers)?
  • what is the state of Mg?
A
  • net flow of current is inward carried by Na, Ca ions
  • Mg enters cell–> blockage
28
Q

at a membrane potential of 20 mV

  • what is the directin of current flow (what ions are driving current)?
  • state of Mg?
A
  • net flow of current is outward carried by K
  • Mg does not enter cell– no channel blockage
29
Q

what AMPAr subunit (and its component) is responsible for mediating LTP?

A
  • GluA1 subunit– interacts with essential proteins via C terminus
30
Q

Pathophysiology of Huntingtons disease (hint: think about HD gene CAG140?
- think about what its effect on hippocampal LTP

A
  • caused by CAG repeats of HD gene
  • leads to polyQ region in polypeptide which causes impaired LTP
31
Q

describe properties of AMPA receptors in terms of their movement in neurons

A
  • highly plastic, change location in response to variety of stimuli
32
Q

qualities of AMPA receptors that enourage efficient synaptic transmission (i.e. receptor stability, receptor pool state)

A
  • reversible receptor stabilization– plastic
  • dynamic equilibrium of receptor pool
33
Q

mechanism of reversible stabilization of AMPA receptors (hint: occurs at post synaptic density)
- what components are involved in this mechanism

A
  • diffusion trapping mediated by extra/intracellular scaffold proteins
34
Q

what is the role of clathrin-dependent endocytosis in AMPA receptor trafficking?
- where does this mechanism take place?

A
  • mediates AMPAr diffusion into PSD
  • extrasynaptic endocytic zones
35
Q

what induces Long term potentiation?

A

bursts of high frequency stimulation (HFS)

36
Q

effect of HFS on NMDA receptors? on CaMKII translocation?

bonus: impact of CaMKII on Y2,Y8 auxiliary AMPAr SU´s?

A
  • HFS relieves Mg block of NMDA receptors– inc. intracell. Ca
  • subsequent CaMKII moved to spines— phosphorylation of AMPAr auxiliary SUs (Y2,Y8)
37
Q

describe the role of AMPAr subunit GluA1 in LTP propagation

A
  • CTD of GluA1 interacts with proteins to stabilize AMPAr
38
Q

effect of swapping GluA1 CTD for GluA2 CTD on LTP?

A
  • impaired LTP, spatial memory performance
39
Q

Effect of ketamine/AMPA-kines on AMPAr?
- clinical applications?

A
  • act as positive allosteric modulators
    — potential antidepressant