week 12 L2: Skeletal neuromuscular junction Flashcards
What is MEPPS?
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
what causes MEPPS ?
ACh released from a single vesicle activates many receptors
What does ACh binding to the nicotinic cation channel do?
channel opens and Na+ flux into cell
local depolarisation at endplate
What is electron microscopy?
reveals vesicle in the apparent act of exocytosis
What does black widow spiders venom influence?
spontaneous transmitter release
What does an increase in MEPPS cause?
muscle spasm, massive ACh release
How can the muscle spasm be reversed?
depletion of vesicles
inhibition on endocytosis (dont endocytose vesicle)
distend terminal
paralysis
What is EPP?
large depolarisation of endplate region of muscle cell
endplate potential
voltages which cause depolarisation
What does a large EPP cause?
a large enough depolarisation activates postsynaptic Na+ channels= AP
What factors contribute to a muscle fibre action potential?
EPP needed above threshold then with the help of Na+, depolarisation in the endplate region can cause a muscle fibre action potential.
What mV does the cell need to depolarise to for Na+ to open? EP
-40mV
What problem is there with the cell attached path technique?
muscle fibre contraction breaks glass microelectrode
What needs to be reduced so cell attached technique can be used on muscle fibre?
need to reduce EPP to study neurally evoked transmitter release.
How to reduce a muscle contraction so it can be analysed?
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
What is the relationship between amplitudes epp and mepp?
the amplitude of epp is a multiple of the amplitude mepp (smallest amplitude)
QUANTAL
What is quantal content (Q.C)?
number of vesicles/stimuli
Quantal Content equation?
(mean EPP amplitude mv) / (mean MEPP amplitude mV)
What does the mean epp amplitude correspond to in the Q.C equation?
in response to motor nerve stimulation
What does the mepp amplitude correspond to in the Q.c equation?
occur spontaneously (without nerve stimulation)
What does quanta mean in the context of NMJ?
release of a vesicle gives a quanta
What does a change in epp and no change in mepp mean?
toxin works pre-synamptiaclly
act pre-synamptically to increase neurally evoked transmitter release
What enzyme is used to covert choline to ACh?
CAT
Choline acetyl transferase
Where does the Acetyl-Co-A come from?
Mitochondria
Where is the choline come from?
from re-uptake from NMJ
What are the precursors for Acetyl choline production?
Acetyl-Co-A and choline
How is Acetyl choline made at the terminal of the presynaptic neurone?
Enzyme CAT coverts acetyl-Co-A to Co-A, adding the acetyl to the choline and synthesise together to make ACh
what is a choline receptor called?
Choline transporter
What is choline re-uptake dependent on?
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
what blocks a Choline transporter?
Hemicholinium 3
What is the impact of Hemicholinium 3?
Less ACh
Amplitude of epp and mepp decreased
No change in quantal content
What drug effects storage?
Vesamicol
How does Vesamicol effect storage?
inhibits ACh vesicular transporter
blocks transport of ACh into vesicle
Less ACh into vesicle
Decrease in epp and mepp, no change Q.C
How does Tetrodotoxin effect the body?
causing paralysis of diaphragm=respiratory failure
similar
What is the source of Tetrodotoxin?
powerful toxin produced by bacteria and concentrated in pufferfish e.g liver
What 4 drugs effect release?
tetrodotoxin, conotoxin, dentrotoxin, Botulinum toxin
How does tetrodotoxin effect release?
blocks Na+ channels (no Na into terminal)
No AP, no release, no EP
How does conotoxins effect release?
Block voltage gated Ca2+ channels
Decrease Ca2+ influx, decrease release
Conotoxin effect on amplitude?
epp decrease
mepp no change
decrease Q.C
Does conotoxin work pre or post synaptically?
pre-synaptically
how does dentrotoxin effect release?
blocks voltage gated K+ channels
prolonged AP, Ca2+ influx, increased release
Dentrotoxin effect on amplitude?
epp increased
no change in mepp
increased QC
What bacterium is Botulinum toxin from?
bacterium clostridium botulinum
What can botulinum toxin lead to?
respiratory paralysis
What muscle disorders can Botulinum clinically treat?
chronic migraine, excessive underarm sweating, neuropathic pain
What is Botulinum also known as?
Botox
How does Botulinum effect release?
Blocks vesicle fusion by cleaving a vesicular protein required for exocytosis, decrease release
Botulinum effect on amplitude?
epp decrease
mepp no change
decrease QC
