T1L7 chemisty and physiology of the synpase

Question 1

2 main categories of receptors

Answer 1

1. ionotropic

2. metabotropic receptors

Question 2

2 families of postsynaptic receptors:

Answer 2

1. ligand gated ion channels
2. g protein coupled receptors
   see pic s7

Question 3

1. ionotropic receptors

Answer 3

• ligand gated ion channels are fast
• ligand = neurotransmitter
• neurotransmitter binds to channel, changing its conformation and opening the pore

Question 4

ionotropic receptor variation

Answer 4

pharmacology:

• agonists
• antagonists

kinetics: the rate of transmitter binding and channel opening

selectivity- which ions are fluxed

conductance

Question 5

agonist and antagonist def

Answer 5

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)

Question 6

fast synaptic transmission and its receptors

Answer 6

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

Question 7

3 glutamate receptors

Answer 7

1. NMDA
2. AMPA
3. Kainate

Question 8

NDMA receptor

Answer 8

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

Question 9

AMPA receptor

Answer 9

ionotropic glutamate receptor
agonist is AMPA
antagonist is CNQX

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

Question 10

kainate receptor

Answer 10

agonist is kainate
antagonist is CNQC

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

Question 11

regulation of NMDA receptor channel opening

Answer 11

• 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)

Question 12

NMDA receptor disregulation

Answer 12

• 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

Question 13

nmda glutamate excitotoxicity

Answer 13

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

Question 14

other ionotropic receptors (ligand gated ion channels0

Answer 14

glutamate (excitatory)
GABAa (inhibitory- brain)
glycine (inhibitory- spine and brainstem)
nicotine (excitatory or modulatory)
serotonin (excitatory or modulatory)
atp (excitatory)

Question 15

2. METABOTROPIC RECEPTORS

Answer 15

• 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

Question 16

synaptic 2ndy messenger systems

Answer 16

maybe see pic s26

Question 17

g proteins mechanism

Answer 17

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

Question 18

types of g protein coupled alpha subunits

Answer 18

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

Question 19

shortcut pathway

2ndry messenger cascades

cAMP, PIP2

Answer 19

receptor > G protein > ion channel
pic s28

see pic s 29, 30, 31

Question 20

kinases and phosphatases

Answer 20

• 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

Question 21

long term effects of neurotransmitters on synapses

Answer 21

• recruit new receptors

Question 22

g protein signal amplification

Answer 22

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

pic s34

Question 23

modulation by receptor activation

Answer 23

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

Question 24

metabotropic receptors

Answer 24

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

Question 25

GABAa vs GABAb

Answer 25

``` a= ionotropic b= metabotropic ```

Question 26

3. other receptors found in or in neurones

Answer 26

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 :)