Neuro - NTs and Pharmacology

Question 1

What features of the nervous system underpin synaptic transmission?

Answer 1

Diversity and plasticity of nervous system

Question 2

What do spines on dendrites do?

Answer 2

Increase surface area

Question 3

What are dendrites concerned with?

Answer 3

Information reception

Question 4

What does the soma do?

Answer 4

Integration of multiple signals form different NTs

Question 5

What is the axon/synaptic terminal involved in?

Answer 5

Rapid transmission of the AP and NT release

Question 6

How fast is neurotransmission?

Answer 6

2ms

Question 7

How wide is a normal synaptic cleft?

Answer 7

20-100nm

Question 8

What are the 3 main stages of synaptic transmission?

Answer 8

1 Biosynthesis
2 Receptor action
3 Inactivation

Question 9

What are the three main molecules that make up NTs?

Answer 9

Amino acids
Amines
Neuropeptides

Question 10

What is an example of NTs that are amino acids

Answer 10

Glutamate
GABA
Glycine

Question 11

What is an example of NTs that are amines

Answer 11

DA

NA

Question 12

What is an example of NTs that are neuropeptides

Answer 12

opioid peptides e.g. endorphins

Question 13

What kinds of effects do NTs evoke?

Answer 13

Rapid or slower effects

Question 14

How many NT influences are received simultaneously by a neurone?

Answer 14

Multiple, which are then integrated into 1 diverse signal in the 2nd cell.

Question 15

How are calcium channels opening in the presynaptic terminal?

Answer 15

From both a sodium influx and potassium efflux as a result of depolarisation from AP

Question 16

What does the intracellular volume of calcium increase to?

Answer 16

from 1µM —-> 200µM

Question 17

What does NT release depend upon?

Answer 17

Calcium dependent and rapid transduction

Question 18

Is neurotransmission active or passive?

Answer 18

Active - requires ATP

Question 19

How are synaptic vesicles filled with NTs?

Answer 19

Protein pumps pump from 4,000 to 10,000 NTs into a vesicle

Question 20

What happens after the influx of calcium?

Answer 20

Vesicles containing NTs dock and are primed at the edge of the knob, but only release when they fuse with the membrane with the help of vesicular proteins.

Question 21

What is the role of vesicular proteins?

Answer 21

Help the fusing of the vesicles with the membrane of the presynaptic terminal

Question 22

What is an example of a vesicular protein?

Answer 22

SNARE proteins: synapsin

Question 23

What is alpha latrotoxin?

Answer 23

Neurotoxin - stimulates NT release until the presynaptic neurone is depleted of NTs

Question 24

Where is alpha latrotoxin found?

Answer 24

Black Widow Spider Venom - causes ACh release and eventual paralysis.

Question 25

What are zinc dependent endopeptidases?

Answer 25

inhibit NT release

Question 26

What is an example of a zinc dependent endopeptidase?

Answer 26

Tetanum toxin from C.Tetani - causes spasms and paralysis as it inhibits GABA and Glycine release which are inhibitory

Question 27

Where is the botulinum toxin come from?

Answer 27

C.Botulinum

Question 28

What is the effect of botulinum toxin?

Answer 28

Causes flaccid paralysis - first part of molecule binds to nerve terminal and the 2nd part penetrates the cholinergic terminal and cleaves the peptide bonds of vesicular proteins to inhibit NT release

Question 29

How does botulism cause death?

Answer 29

Respiratory arrest

Question 30

What is c.botulinum used for commercially?

Answer 30

Botox

Question 31

What are the 2 main classes of receptor?

Answer 31

Ion channel linked | G-protein coupled

Question 32

How fast do ion channel linked receptors act?

Answer 32

Fast (milsecs)

Question 33

How fast do g-protein coupled receptors act?

Answer 33

Slow (seconds to minutes)

Question 34

What do ion-channel linked receptors mediate?

Answer 34

All fast, excitatory and inhibitory transmissions

Question 35

What do G-protein coupled receptors mediate?

Answer 35

All slow reactions

Question 36

What may G-protein coupled receptors be in the form of?

Answer 36

Enzymes or channels

Question 37

What is an example of an ion channel inked receptor?

Answer 37

Glutamate receptor - allows for the opening of sodium channels to allow for depolarisation and propagation of the AP.

Question 38

How do G-protein coupled receptors work?

Answer 38

First couples to the G protein which then links to the effector to induce a response in the effector

Question 39

What is an example of a G-protein coupled receptor?

Answer 39

ACh muscarinic receptors

Question 40

What is the structure of ion channel inked receptors?

Answer 40

5 subunits with distinct properties on each one.

Question 41

What is the glutamate receptor?

Answer 41

Excitatory ion channel inked receptor linked to depolarisation

Question 42

What is the GABA-A receptor?

Answer 42

Inhibitory ion channel inked receptor linked to hyperpolarisation

Question 43

What is the EPSP?

Answer 43

Excitatory post synaptic potential after the binding of glutamate

Question 44

What is the IPSP?

Answer 44

Inhibitory post synaptic potential after the binding of GABA

Question 45

What must there be between the EPSP and is the IPSP?

Answer 45

A balance

Question 46

What is the AMPA receptor?

Answer 46

Type of glutamate receptor

Question 47

What does the AMPA receptor mediate?

Answer 47

Majority of fast excitatory synapses

Question 48

How is the AMPA receptor closely regulated?

Answer 48

Rapid onset, offset and desensitisation

Question 49

What is the NMDA receptor?

Answer 49

Glutamate receptor that's permeable to Calcium as well as Sodium

Question 50

What do NMDA receptors do?

Answer 50

Provide the slow component of excitatory transmission

Question 51

How do NMDA receptors serve as coincidence detectors?

Answer 51

Underlie learning and memory mechanisms (e.g. hippocampus has a high concentration of NMDA receptors)

Question 52

How is glutamate produced?

Answer 52

By glucose via the TCA cycle and transamination in the presynaptic terminal.

Question 53

How does glutamate act as a neurotransmitter?

Answer 53

Reversibly binds to post synaptic receptors to eventually induce a post synaptic response

Question 54

What happens after glutamate binds to receptors?

Answer 54

It is inactivated by reputake into the presynaptic cells and glutamate transports found in glial cells + presynaptic terminal

Question 55

What are EAATs?

Answer 55

Excitatory amino acid transporters

Question 56

What is the glutamate-glutamine cycle?

Answer 56

Glutamate is converted to glutamine via glutamine synthetase. A high concentration of glutamine is then released by glial cells and pumped back into the presynaptic terminal

Question 57

What is commonly associated with excess glutamate found within the synapse?

Answer 57

Seizures

Question 58

How do things return to normal after a seizure?

Answer 58

Glutamate levels slowly fall as it is converted to glutamine

Question 59

How is epilepsy characterised?

Answer 59

Recurrent seizures due to abnormal neuronal excitability

Question 60

How many epilepsy patients are refractory to treatment?

Answer 60

25-30%

Question 61

What do we believe to be the underlying problem with many cases of epilepsy?

Answer 61

GABA transmission (inhibitory) may not be functioning correctly allowing excess glutamate activity to occur

Question 62

How is GABA synthesised?

Answer 62

Decarboxylation of glutamate via glutamic acid decarboxylase in the presynaptic terminal

Question 63

How does GABA cause hyperpolarisation?

Answer 63

Binds to GABA-ARs to induce chloride influx into cells so that the cell is less sensitive to the Action potential, as its MP is brought down lots.

Question 64

What happens to GABA after binding to GABA-A receptors?

Answer 64

Reuptake of GABA via GABA transporters (GATs) in presynaptic terminal or modification by GABATS

Question 65

What are GABATs?

Answer 65

GABA transaminase which modified GABA to succinic semialdehyde which is the converted to succinate for the TCA cycle

Question 66

Where does conversion of GABA to succinic semialdehyde take place?

Answer 66

Typically glial cells, but excess GABA in cells means that the presynaptic terminal will take up some GABA too with GABATS

Question 67

What is the structure of a GABA receptor?

Answer 67

Pentameric

Question 68

How are drugs tailored towards GABA receptor structure

Answer 68

Different drugs can bind got different sub units of GABA A receptor - many of them facilitate GABA transmission to improve its function.

Question 69

What's an example of anti-epileptic drugs?

Answer 69

Barbiturates