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Neuroscience > Receptors > Flashcards

Receptors Flashcards

1
Q

where do receptors coordinate communication?

what is this made up of?

what do they all express?

A

the tripartite synapse

presynaptic terminal
postsynaptic terminal
astrocyte

receptors exclusively involved in coordinating cell signalling events

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2
Q

what is the role of astrocytes and glial cells at the tripartite synapse?

A

control and fine tune communication events within the synapse

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3
Q

what are the 3 receptor types?

A

ion channel
GPCR
tyrosine-kinase receptor

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4
Q

what are ionotropic receptors?

what opens them?

what timescale are they in?

give an example

A

ligand-gated ion channels

the binding of small molecule transmitters or signalling molecules

milliseconds

nicotinic AChR

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5
Q

what is the timescale of metabotropic/GPCRs?

what is their effector?

give 2 examples

A

seconds

enzyme/channel

muscarinic AChR
adrenoreceptors

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6
Q

what is the timescale of kinase-linked receptors?

what is the effector?

give an example of a signalling molecule that activates this

A

minutes

enzyme
- Tyrosine-kinase
(phosphorylates targets of tyrosine residues)

insulin

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7
Q

what is the timescale of the steroid/thyroid type receptors?

what is the effector?

give an example of an activating molecule

A

hours

gene transcription

oestrogen

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8
Q

describe the process of ligand-gated ion channels opening

A
  1. ligand binds to ligand binding domain
  2. changes conformation in receptor structure
  3. opens pore in membrane
  4. ions pass through to drive response
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9
Q

describe the process of GPCR signalling

A
  1. ligand binds to GPCR
  2. induces conformational change in G protein
  3. enables binding of G protein to receptor
  4. stimulates exchange of GDP for GTP on the protein
  5. activates the G protein
  6. dissociation of the alpha beta gamma complex
  7. normally activity driven by alpha subunit

BUT can be mediated by beta-gamma subunit
-> can control channel opening

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10
Q

describe the process of RTK signalling

A
  1. ligand binds to ligand-binding domain
  2. conformational change in protein
    = dimerisation of receptor
  3. activates receptor
  4. kinase domain has TK activity
  5. phosphorylation of tyrosine amino acid residues
  6. residues on the receptor get phosphorylated first
    -> activates receptor to signal downstream
  7. involves binding of adaptor proteins (e.g. MAPK) to receptor
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11
Q

many small molecule neurotransmitters can signal through BOTH…?

A

C-protein coupled receptors
AND
ionotropic ligand-gated ion channels

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12
Q

what are the 3 main effector pathways of GPCR signalling?

A

norepinephrine
- via Gs

glutamate
- via Gq

dopamine
- via Gi

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13
Q

describe what happens when norepinephrine binds to b-adrenergic GPCR

A
  1. induces conformational change in b-adrenergic
  2. recruitment of Gs
  3. exchange of GDP and GTP
  4. activation of G protein -> release of stimulatory alpha subunit
  5. activates adenylyl cyclase
  6. produces cAMP
  7. activates protein kinase A
  8. increases protein phosphorylation of targets (e.g. ion channels, enzymes, TFs)
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14
Q

describe what happens when glutamate binds to mGluR (GPCR)

A
  1. recruits Gq
  2. activates phospholipase C
  3. catalyses production of Diacylglycerol and IP3 by hydrolysing PIP2
  4. Diacylglycerol recruits Protein kinase C
  5. increases protein phosphorylation
  6. IP3 binds to IP3 receptors on intracellular calcium stores (e.g. on ER)
  7. releases Ca2+
  8. activates calcium-binding proteins
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15
Q

describe what happens when dopamine binds to Dopamine D2 (GPCR)

A
  1. recruits Gi (inhibitory)
  2. inhibits adenyl cyclase activity
  3. reduces cAMP
  4. reduction in downstream cAMP signalling events
  5. decrease in protein phosphorylation
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16
Q

describe ionotropic receptor structure

A

different permeabilities

multiple subunits
- can be homomeric, BUT normally heteromeric

17
Q

what are purinoreceptors activated by?

describe their structure

which ions pass through?

A

ATP

trimeric
= 3 subunits

each subunit has 2 transmembrane domains

Na+
Ca2+

18
Q

describe the structure of glutamate receptors

which ions pass through?

A

tetrameric
= 4 subunits

each subunit has 3 transmembrane domains and a re-entrant loop

Na+
Ca2+

19
Q

what are pentameric receptors activated by?

describe the structure

which ions pass through?

A

ACh, GABA, Glycine, Serotonin

pentameric
= 5 subunits

each subunit has 4 transmembrane domains

Na+
Ca2+
Cl-

20
Q

what are the 3 classes of glutamate-gated ionotropic receptors?

what are these sub-divisions based on?

A

AMPA
NMDA
Kainate

their sensitivity to these synthetic ligands

21
Q

what are the 4 subunits of AMPA receptors?

what about the 7 subunits of NMDA receptors?

what are the 5 subunits of the kainate receptors?

A

GluA1-4

GluN1
GluN2a-d
GluN3a-b

GluK1-5

22
Q

what else do the pentamer receptors have in common?

what is the role of this?

give 2 examples

A

a Cys-loop in the N-terminus

coupling agonist binding to channel opening

glycine receptors
GABAa receptors

23
Q

what are the 3 classes of metabotropic glutamate receptors?

what type of system are these involved in?

A 
class I 
class II
class III

second messenger signalling systems
(via GPCR)

24
Q

what second messengers do the 3 classes of metabotropic glutamate receptors signal through?

A 
class I:
excitatory IP3 and Ca2+
class II and III:
inhibition of cAMP
25
Q

what are class II and class III glutamate receptors sometimes referred to as?

why?

A

autoreceptors

they can be found on the pre-synaptic nerve terminal
- sense glutamate to modulate further NT release

26
Q

what are the gene families in the metabotropic glutamate families?

A 
class I:
mGluR1 + mGluR5
class II:
mGluR2 + mGluR3
class III:
mGluR4 + mGluR6-8
27
Q

what do iGluRs work in combination to produce?

describe how AMPA and NDMA receptors are involved in this

A

excitatory postsynaptic potential (EPSP)

at a glutamatergic synapse:

  1. glutamate released
  2. activation of AMPAR
  3. ion flow across membrane
  4. rapidly desensitises AMPAR
  5. depolarisation of membrane
  6. activates NMDAR
  7. allows Ca2+ through channel
28
Q

what does ACh have a predominantly modulatory effect on?

what are the 2 classes of ACh receptor?

A

brain function

muscarinic
nicotinic

29
Q

what type of channels are muscarinic and nicotinic receptors?

what are their selective agonists and antagonists?

A

muscarinic:
GPCR

  • agonist = muscarine
  • antagonist = atropine

nicotinic:
LGIC

  • agonist = nicotine
  • antagonist = tubocurarine
30
Q

what are the subdivisions of muscarinic ACh receptors?

which G protein do they signal via?

A

M1, M3, M5
via Gq

M2, M4
via Gi

31
Q

what are the key effectors of M1, M3, M5?

what does this result in?

A

increased:
phospholipase C
[Ca2+]
MAP kinases

decreased:
M current

increased activity

32
Q

what are the key effectors of M2 and M4?

what does this result in?

A

increased:
MAPK
GIRK channels

decreased:
adenylyl cyclase
voltage-gated C2+ channels

decreased activity

33
Q

describe the structure of nAChRs

how many ACh molecules are required to open the pore?

A

pentameric LGIC receptors

Cys-loop receptors

5-membrane spanning subunits form a central pore

2 molecules

34
Q

what do the multiple genes coding for nAChR subunits enable?

what is the most abundant nAChRs in the brain?

which subunits dictate the ACh binding sites?

A

different subunit combinations producing different nAChR subtypes

homomeric alpha7 nAChRs
heteromeric a4b2 nAChRs

alpha subunits

35
Q

describe the features of a GABA A receptor

A

pentameric receptor

cys-loop

4 transmembrane domains

M2 domain lines channel to determine permeability to ions
- normally a Cl- conductance
-> polarises the membrane
= inhibitory

36
Q

how does the GABA B receptor act?

A

B1 and B2 subunits heterodimerise

  • > couple with Gi
  • > releases beta-gamma subunit
  • > inhibits adenylyl cylase

= activation of K+ channels or inhibition of Ca2+ channels

37
Q

what are all dopamine receptors?

what are the 2 sub-types and what are they coupled to?

what are the receptors in these groups?

A

GPCRs

D1-like (coupled to G-alpha s)
D2-like (coupled to G-alpha i)

D1-like
= D1 + D5

D2-like
= D2, D3 + D4

38
Q

explain what happens when dopamine receptors heterodimerise

A
  1. activate Gq
  2. activates PLC
  3. produces IP3
    - > Ca2+ release

also produces DAG
-> activates PKC

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