week 12 L2: Skeletal neuromuscular junction

Question 1

What is MEPPS?

Answer 1

Miniature end plate potentials
Can summate to cause a EPP caused by the random release of single quanta of neurotransmitter from a resting presynaptic terminal

Question 2

what causes MEPPS ?

Answer 2

ACh released from a single vesicle activates many receptors

Question 3

What does ACh binding to the nicotinic cation channel do?

Answer 3

channel opens and Na+ flux into cell

local depolarisation at endplate

Question 4

What is electron microscopy?

Answer 4

reveals vesicle in the apparent act of exocytosis

Question 5

What does black widow spiders venom influence?

Answer 5

spontaneous transmitter release

Question 6

What does an increase in MEPPS cause?

Answer 6

muscle spasm, massive ACh release

Question 7

How can the muscle spasm be reversed?

Answer 7

depletion of vesicles
inhibition on endocytosis (dont endocytose vesicle)
distend terminal
paralysis

Question 8

What is EPP?

Answer 8

large depolarisation of endplate region of muscle cell
endplate potential
voltages which cause depolarisation

Question 9

What does a large EPP cause?

Answer 9

a large enough depolarisation activates postsynaptic Na+ channels= AP

Question 10

What factors contribute to a muscle fibre action potential?

Answer 10

EPP needed above threshold then with the help of Na+, depolarisation in the endplate region can cause a muscle fibre action potential.

Question 11

What mV does the cell need to depolarise to for Na+ to open? EP

Answer 11

-40mV

Question 12

What problem is there with the cell attached path technique?

Answer 12

muscle fibre contraction breaks glass microelectrode

Question 13

What needs to be reduced so cell attached technique can be used on muscle fibre?

Answer 13

need to reduce EPP to study neurally evoked transmitter release.

Question 14

How to reduce a muscle contraction so it can be analysed?

Answer 14

use a buffered solution of high ratio of Mg:Ca

magnesium blacks the Ca2+ channels, so just mepp occurs not a high enough EPP for a contraction

Question 15

What is the relationship between amplitudes epp and mepp?

Answer 15

the amplitude of epp is a multiple of the amplitude mepp (smallest amplitude)
QUANTAL

Question 16

What is quantal content (Q.C)?

Answer 16

number of vesicles/stimuli

Question 17

Quantal Content equation?

Answer 17

(mean EPP amplitude mv) / (mean MEPP amplitude mV)

Question 18

What does the mean epp amplitude correspond to in the Q.C equation?

Answer 18

in response to motor nerve stimulation

Question 19

What does the mepp amplitude correspond to in the Q.c equation?

Answer 19

occur spontaneously (without nerve stimulation)

Question 20

What does quanta mean in the context of NMJ?

Answer 20

release of a vesicle gives a quanta

Question 21

What does a change in epp and no change in mepp mean?

Answer 21

toxin works pre-synamptiaclly

act pre-synamptically to increase neurally evoked transmitter release

Question 22

What enzyme is used to covert choline to ACh?

Answer 22

CAT

Choline acetyl transferase

Question 23

Where does the Acetyl-Co-A come from?

Answer 23

Mitochondria

Question 24

Where is the choline come from?

Answer 24

from re-uptake from NMJ

Question 25

What are the precursors for Acetyl choline production?

Answer 25

Acetyl-Co-A and choline

Question 26

How is Acetyl choline made at the terminal of the presynaptic neurone?

Answer 26

Enzyme CAT coverts acetyl-Co-A to Co-A, adding the acetyl to the choline and synthesise together to make ACh

Question 27

what is a choline receptor called?

Answer 27

Choline transporter

Question 28

What is choline re-uptake dependent on?

Answer 28

Na+ dependent. If Na+is at high concentration in terminal then an AP is occurring so more ACh is needed. voltage dependent, Na+ creates a depolarisation in terminal

Question 29

what blocks a Choline transporter?

Answer 29

Hemicholinium 3

Question 30

What is the impact of Hemicholinium 3?

Answer 30

Less ACh Amplitude of epp and mepp decreased No change in quantal content

Question 31

What drug effects storage?

Answer 31

Vesamicol

Question 32

How does Vesamicol effect storage?

Answer 32

inhibits ACh vesicular transporter blocks transport of ACh into vesicle Less ACh into vesicle Decrease in epp and mepp, no change Q.C

Question 33

How does Tetrodotoxin effect the body?

Answer 33

causing paralysis of diaphragm=respiratory failure | similar

Question 34

What is the source of Tetrodotoxin?

Answer 34

powerful toxin produced by bacteria and concentrated in pufferfish e.g liver

Question 35

What 4 drugs effect release?

Answer 35

tetrodotoxin, conotoxin, dentrotoxin, Botulinum toxin

Question 36

How does tetrodotoxin effect release?

Answer 36

blocks Na+ channels (no Na into terminal) | No AP, no release, no EP

Question 37

How does conotoxins effect release?

Answer 37

Block voltage gated Ca2+ channels | Decrease Ca2+ influx, decrease release

Question 38

Conotoxin effect on amplitude?

Answer 38

epp decrease mepp no change decrease Q.C

Question 39

Does conotoxin work pre or post synaptically?

Answer 39

pre-synaptically

Question 40

how does dentrotoxin effect release?

Answer 40

blocks voltage gated K+ channels | prolonged AP, Ca2+ influx, increased release

Question 41

Dentrotoxin effect on amplitude?

Answer 41

epp increased no change in mepp increased QC

Question 42

What bacterium is Botulinum toxin from?

Answer 42

bacterium clostridium botulinum

Question 43

What can botulinum toxin lead to?

Answer 43

respiratory paralysis

Question 44

What muscle disorders can Botulinum clinically treat?

Answer 44

chronic migraine, excessive underarm sweating, neuropathic pain

Question 45

What is Botulinum also known as?

Answer 45

Botox

Question 46

How does Botulinum effect release?

Answer 46

Blocks vesicle fusion by cleaving a vesicular protein required for exocytosis, decrease release

Question 47

Botulinum effect on amplitude?

Answer 47

epp decrease mepp no change decrease QC