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Module 202 > T1L7 chemisty and physiology of the synpase > Flashcards

T1L7 chemisty and physiology of the synpase Flashcards

1
Q

2 main categories of receptors

A
  1. ionotropic

2. metabotropic receptors

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2
Q

2 families of postsynaptic receptors:

A
  1. ligand gated ion channels
  2. g protein coupled receptors
    see pic s7
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3
Q
  1. ionotropic receptors
A
  • ligand gated ion channels are fast
  • ligand = neurotransmitter
  • neurotransmitter binds to channel, changing its conformation and opening the pore
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4
Q

ionotropic receptor variation

A

pharmacology:

  • agonists
  • antagonists

kinetics: the rate of transmitter binding and channel opening

selectivity- which ions are fluxed

conductance

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5
Q

agonist and antagonist def

A

agonist- a drug that can combine with a receptor on a cell to produce a physiological reaction

antagonist- a drug that blocks the activity of the agonist or endogenous ligand (neurotransmitter)

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6
Q

fast synaptic transmission and its receptors

A

glutamate ionotropic receptors generally flux na.
- na flux causes a EPSP (excitatory post synaptic potential) which depolarises postsynaptic neuron. THIS ACTIVATED THE NEURON TO FIRE

gaba ionotropic receptors flux cl-
- cl- flux causes an IPSP (inhibitory postsynaptic potential) which hyperpolarises postsynaptic membrane. THIS INHIBITS THE NEURON TO FIRE

acetylcholine, serotonin and atp also activate ionotropic receptors

it is the integration of all these changes that dictate if an action potential will fire or not

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7
Q

3 glutamate receptors

A
  1. NMDA
  2. AMPA
  3. Kainate
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8
Q

NDMA receptor

A

ionotropic glutamate receptor
agonist is NMDA
antagonist is APV

  • slow opening
  • permeable to na, k, ca
    BUT
    requires extracellular glycine as cofactor
  • also voltage gated (opens when membrane depolarises)
  • late phase EPSP
  • activated only in an already depolarised membrane in the presence of glutamate
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9
Q

AMPA receptor

A

ionotropic glutamate receptor
agonist is AMPA
antagonist is CNQX

  • fast opening
  • permeable to na and k
  • early phase epsp
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10
Q

kainate receptor

A

agonist is kainate
antagonist is CNQC

  • fast opening
  • permeable to na and k
  • early phase epsp
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11
Q

regulation of NMDA receptor channel opening

A
  • epsps are measured from resting potential higher than mg blockade. in presence or absecnce of AMPA OR NMDA antagonists.
  • slower kinetics of nmda late phase epsp

the influx of ca2+ as well as na leads to activation of enzymes and intracellular signalling that causes widespread changes in postsynaptic cell (neuroplasticity)

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12
Q

NMDA receptor disregulation

A
  • nmda receptors inhibited by phencyclidine and MK801 (both bind to open pore)
  • this produces hallucinations similar to schizophrenia
  • some antipsychotics enhance flow through nmda pores
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13
Q

nmda glutamate excitotoxicity

A
  • excess ca influx into cell
  • overactivates enzymes that degrade proteins, lipids, nucleic acids
  • this cell damage occurs after cardiac arrest, stroke, repeated intense seizures
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14
Q

other ionotropic receptors (ligand gated ion channels0

A 
glutamate (excitatory)
GABAa (inhibitory- brain)
glycine (inhibitory- spine and brainstem)
nicotine (excitatory or modulatory)
serotonin (excitatory or modulatory)
atp (excitatory)
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15
Q
  1. METABOTROPIC RECEPTORS
A
  • Signals transduced into cell via g proteins which trigger intracellular events leading to channel opening

g protein coupled receptors (GPRCs)

  • multiple receptors for every neurotransmitter
  • transmitter binds to extracellular portion
  • this binding triggers uncoupling of heteromeric g protein
  • transduces signal across membrane
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16
Q

synaptic 2ndy messenger systems

A

maybe see pic s26

17
Q

g proteins mechanism

A

3 subunits: alpha, beta, gamma

  • at rest heteromer is bound to gdp
  • when ligand binds, GDP>GTP and heteromer is split into the alpha and gamma subunits

alpha subunits have GTP>GDP enzymatic action, which stops the reaction

18
Q

types of g protein coupled alpha subunits

A

alpha:
Gs stimulates adenylyl cyclase
Gi inhibits adenylyl cyclase
Gq stimulates phospholipase C

beta:

  • activate k+ channels directly
  • this is mode of action for muscarinic aCh receptors in heart and GABAb receptor
19
Q

shortcut pathway

2ndry messenger cascades

cAMP, PIP2

A

receptor > G protein > ion channel
pic s28

see pic s 29, 30, 31

20
Q

kinases and phosphatases

A
  • activity of many proteins regulated by their phosphorylation state
  • maintainance of p state is important for control

phosphorylation gated channels can influence membrane potential and excitation state

21
Q

long term effects of neurotransmitters on synapses

A
  • recruit new receptors
22
Q

g protein signal amplification

A
  • one transmitter bound receptor can uncouple multiple heteromers
  • signal amplified at every stage

pic s34

23
Q

modulation by receptor activation

A

presynaptic receptors - change amount of transmitter released:

  • autoreceptors - regulate release of transmitter by modulating its synthesis, storage, or reuptake
  • heteroreceptors - regulated synthesis and release of neurotransmitters other than their own ligand ie NE can influence aCH release by modulating a-adrenergic receptors

postsynaptic receptors- change firing pattern of activity

  • increase or decrease rate of cell firing (either directly by action at ligand gated ion channels or indirectly at g protein or phosphorylation coupled channels
  • long term synaptic changes
24
Q

metabotropic receptors

A

group I: mGluR1+5 (Gq)
group II: mGluR2+3 (Gi)
group III: mGLuR4+6+7+8 (Gi)

GABAb receptors
muscarinic acetylcholine receptors
dopamine receptors
adrenaline and noradrenaline receptors
serotonin receptors
neuropeptide receptors
25
Q

GABAa vs GABAb

A 
a= ionotropic
b= metabotropic
26
Q
  1. other receptors found in or in neurones
A
  1. enzyme linked receptors:
    - eg receptor tyrosine kinase
    - transmembrane proteins with intrinsic tyrosine kinase activity activated by neurotrophin binding (eg NGF)
    - on activation autophosphorylate
  2. membrane permeant signalling molecules activate intracellular receptors

see pic on s38 is v helpful :)

Module 202 (49 decks)

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