T1 L7 Chemistry & physiology of the synapse

Question 1

What are the 4 main types of transmitters?

Answer 1

Amino acids
Monoamines
Acetylcholine
Neuropeptides

Question 2

What is a ligand?

Answer 2

Neurotransmitter

Binds to the channel, changing its conformation to open it & allow ions to flux through the central pore

Question 3

What is the definition of pharmacology?

Answer 3

What transmitter binds to the receptor & how drugs interact with them

Question 4

What is an agonist?

Answer 4

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

Question 5

What is an antagonist?

Answer 5

A drug that blocks the activity of the agonist or endogenous ligand

Question 6

What is the definition of kinetics?

Answer 6

Rate of transmitter binding & channel gating determine the duration of their effects

Question 7

What is the definition of selectivity?

Answer 7

What ions are fluxed

Question 8

What is the definition of conductance?

Answer 8

The rate of flux helps determine effect magnitude

Question 9

What do glutamate ionotropic receptors do?

Answer 9

Flux Na+

Causes an EPSP depolarising the postsynaptic neuron

Question 10

What do GABA ionotropic receptors do?

Answer 10

Flux Cl-
Causes an IPSP hyper polarising the postsynaptic neuron
Inhibits the neuron from firing unless there is sufficient glutamate stimulation to counteract the hyperpolarisation

Question 11

What else can activate ionotropic receptors?

Answer 11

Acetylcholine
Serotonin
ATP

Question 12

What activates nicotinic receptors?

Answer 12

Acetylcholine

Question 13

What happens when nicotinic receptors are activated?

Answer 13

Excitation & contraction of muscle cells

Question 14

What 3 types of ionotropic receptors respond to glutamate?

Answer 14

NMDA
AMPA
Kainate

Question 15

What is the agonist & antagonist for NMDA receptors

Answer 15

Agonist - NMDA

Antagonist - APV

Question 16

What is the agonist & antagonist for AMPA receptors?

Answer 16

Agonist- AMPA

Antagonist - CNQX

Question 17

What is the agonist & antagonist for kainate receptors?

Answer 17

Agonist - kainic acid

Antagonist - CNQX

Question 18

What is APV?

Answer 18

An antagonist to NMDA receptors

Question 19

Describe non-NMDA receptors

Answer 19

Fast opening channels permeable to Na+ & K+

Responsible for early phase EPSP

Question 20

Describe the NMDA receptor

Answer 20

Slow opening channel
Requires extracellular glycine as a cofactor to open the channel
Gated by membrane voltage

Question 21

Describe the gating of the NMDA receptor

Answer 21

Mg2+ plugs pore at resting membrane potential
When membrane depolarises, Mg2+ is ejected from the channel by electrostatic repulsion allowing conductance of other cations, activity-dependent synaptic modification

Question 22

Describe the link between NMDA receptors & schizophrenia

Answer 22

NMDA receptors are inhibited by phencyclidine & MK801

Blockade of NMDA receptors in this way produces symptoms that resemble hallucinations associated with Schizophrenia

Question 23

Describe glutamate excitotoxicity

Answer 23

Excessive calcium influx into the cell activates calcium-dependent enzymes that degrade proteins, lipids & nucleic acids

Question 24

When does glutamate excitotoxicity cell damage occur?

Answer 24

After a cardiac arrest
Stroke
Oxygen deficiency
Repeated intense seizures

Question 25

What are some other examples of ionotropic receptors?

Answer 25

Glutamate - excitatory GABA(A) - inhibitory (brain) Glycine - inhibitory (spinal cord & brain stem) Nicotine - excitatory at NMJ. Excitatory or modulatory in CNS Serotonin - excitatory or modulatory ATP - excitatory

Question 26

How do metabotropic receptors work?

Answer 26

Transduce signals into the cell through activation of a G-protein which triggers a series of intracellular evens

Question 27

Describe G-protein coupled receptors

Answer 27

7 transmembrane domain protein Transmitter binds to extracellular domain & triggers uncoupling of a heteromeric G-protein on intracellular surface Transduce signal across cell membrane

Question 28

Give the steps of G-proteins

Answer 28

1) In resting state the heteromer is bound to GDP 2) on binding of a ligand to the receptor the GDP is switched to GTP & heteromer splits in 2 3) Ga subunit & Gby complex divide & diffuse separately through membrane 4) individual parts are able to stimulate activity of other effector proteins 5) a subunits have intrinsic GTP-GDP enzymatic activity allowing the signal to be transient. The breakdown from GTP to GDP switches off its activity 6) Heteromer recomplexes & awaits activation by ligand binding to another receptor

Question 29

Describe the alpha subunit system

Answer 29

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

Question 30

Describe the By complex system

Answer 30

Activate K+ channels directly | Mode of action for muscarinic acetylcholine receptors in heart & GABA(B) receptor

Question 31

Give the steps of the PIP2 second messenger cascade

Answer 31

1) Gq activates phospholipase C 2) Converts PIP2 into IP3 & DAG 3) DAG activates PKC IP3 releases Ca2+ from internal stores which activates Ca2+ dependent enzymes

Question 32

What does protein kinase do?

Answer 32

Phosphorylates a protein

Question 33

What is the purpose of amplification of G-protein signalling?

Answer 33

Provides a method of amplifying signals between neurons

Question 34

How are G-protein signals amplified

Answer 34

1 transmitter bound receptor can uncouple multiple G-protein heteromers Signal can be amplified at every stage A weak signal at the synapse can cause an amplified response in the postsynaptic cell

Question 35

What effect do autoreceptors have on presynaptic receptors?

Answer 35

Regulate release of transmitter by modulating its synthesis, storage, release or reuptake

Question 36

What effect do heteroceptors have on presynaptic receptors?

Answer 36

Regulate synthase and/or release of transmitter

Question 37

How can NE influence the release of ACh?

Answer 37

By modulating alpha-adrenergic receptors

Question 38

Give examples of metabotropic receptors

Answer 38

``` Metabotropic glutamate receptors GABA(B) receptors Muscarinic acetylcholine receptors Dopamine receptors Noradrenergic & adrenergic receptors Serotonin receptors Neuropeptide receptors ```

Question 39

What are receptor tyrosine kinases?

Answer 39

Transmembrane proteins with intrinsic tyrosine kinase activity activated by neurotrophin binding

Question 40

What happens on activation of receptor tyrosine kinases?

Answer 40

On activation they autophosphorylate Phosphorylate intracellular regulatory subunits Signal transduction cascades