Chemistry and physiology of synapse

Question 1

What are the two types of post-synaptic receptors?

Answer 1

Ionotropic

Metabotropic

Question 2

How do ionotropic channels work?

Answer 2

ligand gated ion channels. ligand binds, changes conformation and opens central pore to ions

Question 3

What influx do glutamate ionotropic receptors cause?

Answer 3

Na influx causing an excitatory post synaptic potential EPSP

Question 4

What influx do GABA ionotropic receptors cause?

Answer 4

Cl influx causing inhibitory post synaptic potential

Question 5

What are the 3 types of glutamate ionotropic receptors and what are their agonists?

Answer 5

NMDA- NMDA
AMPA- AMPA
Kaintate- Kainic acid

Question 6

What are the non-NMDA ionotropic channels and how do they act?

Answer 6

AMPA and kainate

FAST opening channels permeable to Na and K. responsible for early phase EPSP

Question 7

What are the NMDA ionotropic channels and how do they act?

Answer 7

NMDA
SLOW opening channels permeable to Na, K and Ca
Also requires cofactor glycine to open channel
Pore is gated by membrane voltage as Mg blocks pore- only removed on depolarisation therefore only activated in already depolarised membrane. Responsible for late phase EPSP

Question 8

Describe nicotinic receptors

Answer 8

Type of ionoptropic receptor located at neuromuscular junction
Activation by Ach causing depolarisation and contraction of muscle cells

Question 9

How are NMDA receptors dysregulated in schizophrenia

Answer 9

NMDA-R inhibited by phenylcyclidine and MK801 which both bind in open pore
blockage causes symptoms resembling hallucinations in schizophrenia
antipsychotic drugs enhance current flow through NMDA channels

Question 10

How do metabotropic receptors work?

Answer 10

Transduce signal by activating G protein which triggers intracellular events

Question 11

What metabotropic receptor does norepinephrine bind to and what G protein does it activate?

Answer 11

b-adrenergic receptor

G alpha S

Question 12

What metabotropic receptor does glutamate bind to and what G protein does it activate?

Answer 12

mGlu receptor

G alpha q

Question 13

What metabotropic receptor does dopamine bind to and what G protein does it activate?

Answer 13

D2 receptor

G alpha i

Question 14

What is the signalling cascade for G alpha s?

Answer 14

adenylyl cyclase activated –> increase cAMP –> activated protein kinase A –> increased protein phosphorylation

Question 15

What is the signalling cascade for G alpha i?

Answer 15

adenylyl cylcase decreased –> decreases cAMP –> does not activate protein kinase A –> reduced protein phosphorylation

Question 16

What is the signalling cascade for G alpha q?

Answer 16

activates phospholipase C –> activated DAG and IP3 –> causes Ca release and activated protein kinase C –> increased protein phosphorylation and activated calcium binding proteins

Question 17

What is the shortcut pathway in metabotropic receptors?

Answer 17

beta-gamma subunit can activate ion channels directly causing fast acting local effect. for example activating L+ channels in muscarinic Ach receptors in the heart

Question 18

How do presynaptic receptors modulate receptor activation?

Answer 18

1. autoreceptors: regulate neurotransmitter release by modulating synthesis, storage, release or uptake.
2. heteroreceptors: axoaxonic or extrasynaptic connections. regulate synthesis/release of NTs other than their own ligand

Question 19

How do postsynaptic receptors modulate receptor activation

Answer 19

change the firing pattern or activity
increase or decrease rate of firing
long term synaptic changes