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Module 202 Theme 1 > Chemistry and physiology of the synapse > Flashcards

Chemistry and physiology of the synapse Flashcards

1
Q

How do the two families of postsynaptic receptor differ?

A

Post synaptic potentials with different time courses
Ion channels vs g protein coupled
Ionotropic and Metabotropic

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2
Q

Describe ionotropic receptors

A

Ligand gated ion channels
Fast transmission
Opened by ligand (neurotransmitter) binding rather than voltage changes
Channels made of 4 or 5 subunits that fold together to form a central pore

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3
Q

What is an agonist?

A

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

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4
Q

What is an antagonist?

A

A drug that blocks the activity of the agonist or endogenous ligand (neurotransmitter)

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5
Q

Describe kinetics

A

Rate of transmitter binding and channel gating determines on duration of their effects

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6
Q

Describe selectivity

A

What ions are fluxed

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7
Q

What is conductance?

A

The rate of flux helps determine effect magnitude

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8
Q

Describe how glutamate ionotropic receptors work

A

Glutamate ionotropic receptors in general flux Na+, which causes an EPSP (Excitatory Post Synaptic Potential) depolarizes the postsynaptic neuron. Enough depolarization, due to multiple receptors being activated or repeated activation, can cause the postsynaptic cell to fire an action potential.

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9
Q

Describe how GABA ionotropic receptors work?

A

GABA ionotropic receptors flux Cl-, which causes an IPSP (Inhibitory Post Synaptic Potential) hyperpolarize the postsynaptic neuron. This inhibits the neuron from firing unless there is sufficient glutamate stimulation to counteract the hyperpolarization.

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10
Q

Name some other neurotransmitters which have ionotropic receptors

A

Acetylcholine
Serotonin
ATP

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11
Q

What activity causes muscle contraction?

A

Activation of nicotinic receptors by acetylcholine

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12
Q

What decides whether or not the postsynaptic neuron will fire an action potential?

A

An integration of all the changes in membrane potential

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13
Q

Which 3 types of ionotropic receptors respond to glutamate?

A

NMDA
AMPA
Kainate

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14
Q

What is the agonist of the NMDA receptor?

A

NMDA

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15
Q

What is the antagonist of the NMDA receptor?

A

APV

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16
Q

What is the agonist of AMP receptors?

A

AMPA

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17
Q

What is the antagonist of AMP receptors?

A

CNQX

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18
Q

What is the agonist of Kainate receptors?

A

Kainic acid

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19
Q

What is the antagonist of the Kainate receptor?

A

CNQX

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20
Q

Which ions are permeable in non-NMDA receptors?

A

Na+ and K+

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21
Q

When is NMDA receptor activated?

A

Activated only in an already depolarized membrane in the presence of glutamate

22
Q

Which ions is a NMDA receptor permeable to?

A

Slow opening channel – permeable to Ca2+ as well as Na+ and K+

23
Q

Which cofactor is required for NMDA receptor to work?

A

Glycine

24
Q

How is NMDA receptor kept at resting potential?

A

it is also gated by membrane voltage – Mg2+ ion plugs pore at resting
membrane potentials. When membrane depolarizes Mg2+ ejected from
channel by electrostatic repulsion allowing conductance of the other
cations, activity-dependent synaptic modification.

25
Q

What are NMDA receptors responsible for?

A

NMDA receptors responsible for a late phase EPSP

26
Q

What does an influx of Ca2+ and Na+ lead to?

A

Activation of enzymes and cellular events causing neuroplasticity - long term memory formation

27
Q

What can go wrong with the NMDA receptor?

A

Schizophrenia - Receptor inhibited by phencyclidine and MK801. Blockade results in hallucinations

Glutamate excitotoxicity- excessive Ca2+ influx into the cell which activates calcium dependant enzymes that degrade proteins, lipids and nuclei acids -
This kind of cell damage occurs after cardiac arrest, stroke, oxygen deficiency, and repeated intense seizures (status epilepticus).

28
Q

Is glutamate excitatory or inhibitory?

A

Excitatory

29
Q

Is GABAa excitatory or inhibitory?

A

Inhibitory

30
Q

Is glycine inhibitory or excitatory?

A

Inhibitory

31
Q

Is nicotine excitatory or inhibitory?

A

excitatory at NMJ (neuromuscular junction)

excitatory or modulatory in the CNS

32
Q

Is serotonin excitatory or inhibitory?

A

Excitatory or modulating

33
Q

Is ATP excitatory or inhibitory?

A

Excitatory

34
Q

How do metabotropic receptors work?

A

They transduce signals into the cell not directly through an ion channel but through activation of a G-protein which in turn triggers a series of intracellular events (that can lead to ion channel opening)

35
Q

Where does the transmitter bind to on a metabotropic receptor?

A

Extracellular domain

36
Q

What does binding of a transmitter to a metabotropic receptor cause?

A

binding triggers uncoupling of
a heteromeric G-protein
on the intracellular surface
transduces signal across the cell membrane

(1) in resting state the heteromer is bound to GDP
(2) on binding of a ligand to the receptor the GDP is switched for a GTP and the heteromer splits in two

(3) the Ga subunit and Gbg complex divide and diffuse separately through the membrane
(4) these individual entities 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 break down from GTP to GDP switches off its activity
(6) at this point the heteromer recomplexes and awaits activation by ligand binding to another receptor.

37
Q

Describe the shortcut pathway

A

Receptor
G protein
Ion channel

38
Q

Describe the second messenger cascade of cAMP

A

Gs and Gi have opposite effects on adenylyl cyclase, thus stimulating or inhibiting the synthesis of cAMP and the subsequent activation of protein kinase A (PKA).

39
Q

Describe the second messenger cascade of PIP2

A

Gq activates phospholipase C (PLC) which converts PIP2 into IP3 and diacylglycerol (DAG). DAG activates protein kinase C (PKC) and IP3 releases Ca2+ from internal stores which activates Ca2+-dependent enzymes

40
Q

How are many proteins regulated?

A

States of phosphorylation

Influences membrane potentials and affects excited state

41
Q

What are long term synaptic changes?

A

structural and biochemical
recruitment of new receptors
Can have very long term consequences eg. long term memory

42
Q

What is meant by amplification?

A

G-protein signalling provides a
method of amplifying signals between neurons

one transmitter bound receptor can uncouple multiple G-protein heteromers

the signal can be amplified at every stage.

what begins as a weak signal at the synapse can cause an amplified response in the postsynaptic cell

43
Q

How does modulation occur by receptor activation in presynaptic receptors?

A

Change in amount of transmitter released

44
Q

What do autoreceptors do?

A

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

45
Q

What dp heteroreceptors fo?

A

Regulate synthesis and or release of transmitters other than their own ligand

46
Q

How does modulation occur by receptor activation in postsynaptic receptors?

A

change firing pattern or activity

increase or decrease rate of cell firing (directly by action at ligand gated ion channels or indirectly G -protein or phosphorylation-coupled channels) long term synaptic changes

47
Q

Give some examples of metabotropic receptors

A

metabotropic glutamate receptors

GABA(B) receptor

muscarinic acetylcholine receptors

dopamine receptors

noradrenergic and adrenergic receptors

serotonin receptors

neuropeptide receptors

48
Q

Give an example of an enzyme linked receptor

A

Receptor tyrosine kinase

49
Q

What is a receptor tyrosine kinase activated by?

A

Neurotrophin binding

50
Q

What happens when tyrosine kinase is activated?

A

Autophosphorylation
Phosphorylate intracellular regulatory subunits
Signal transduction cascades

51
Q

Give an example of Membrane permeant signaling molecules activate intracellular receptors.

A

Nitrogen oxide

Module 202 Theme 1 (28 decks)

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