Neuromuscular Junctions Flashcards
NMJ are..
stable throughout life but are also dynamic. They can ressurrect themselves in response to injury
By the end of the life cycle of NMJ it is found that mainly 1 neuron…
can supply and bind to many effector muscles
Sprouting is where
One neuron binds and attaches to another muscle
The neuron consists of….
the soma, the axon and finally the synapse.
Motor neuron disease is a process where
synaptic connections degenerate. It hits the NMJ’s then goes to the motor neurons in the spinal cords to degrade
the cytoplasmic volume of the axon and the synaptic terminals exceeds…
the volume of the somato-dendritic compartment . by thousands of fold
neuromuscular junctions trigger and sustain…
muscle contractile force. A higher frequency will produce a tetanus unlike a 1Hz frequency
axons break up across the neuron and those branches end up at…
Neuromuscular Junctions
Motor units are intermingled and vary in size
by 5-10 fold
The NMJ comprises of 4 cell types…
- Kranocytes
- Axon
- Terminal Schwann cell
- Muscle fibre
The motor nerve terminal contains
Mitochondria and smooth synaptic vesicles
Excitation contraction coupling occurs when
acetylcholine binds to the receptors on the motor end plate. This causes …..
Steps of Motor neuron formation are as follows
(attach pic)
Acetylcholine receptors cluster
when a nerve terminal binds to a muscle and agrin influences the receptors to be positioned there
Motor Neurone death is a normal part…
of prenatal development
Neonatal muscles are polyneuronally…
innervated
Synapse elimination involves
progressive retraction and takeover of NMJ
in rodents, polyinnervation is eliminated by…
2-4 weeks
Neurones retract some of their neurones while…
stabilising others
Motor unit sizes can be estimated from…
isometric forces
Motor units size decreases…
postnatally
Synapse elimination is part of…
post natal development
synaptic elimination is likely to be
a competitive factor which causes it to happen
Laser ablation of one input leads to…
takeover by the other
There is evidence which shows competition and programmed withdrawal in terms of
synaptic elimination
Synapse elimination is influenced by
activity
Activity dependent rewiring may depend on competition for
neurotrophic factors.
Single action potential produces muscle
contraction
Synaptic activity can be recorded with…
intracellular microelectrodes
Action potentials are triggered when
end plate potentials cross the firing threshold
NMJ’s reliably trigger and sustain
muscle contractile force
During depolarisation of nerve terminal, voltage gated sodium channel allow current to flow in which lead to activation of
voltage gated calcium channels
When calcium enters the cell, it increases the chances
of synaptic vesicles releasing neurotransmitter
The potassium channels which are later activated after depolarisation are designed to…
repolarise the membrane
Acetylcholine receptors associate and aggregate with…
scaffold proteins
Ach receptor are
ligand gated ion channels
The more acetylcholine receptors are activated…
the higher the current (epc)
Acetylcholinesterase is found at
the neuromuscular junction
Acetylcholine is broken down to
choline and acetate. Choline is reabsorbed back.
Acetylcholinesterases increases
The EPP amplitude
hemicholinium inhibits…
the uptake of choline
botulinium blocks the
exocytosis of acetylcholine
Neuromuscular synaptic strength is determined by
number of vesicles contains neurotransmitter released from motor nerve terminals (quantal content) and the magnitude of each vesicles effect on motor end plates
Quantal analysis equation is
m=n x p (m=quant. of transmitter released) (n=number of vesicles available) (p= probability of vesicle exocytosis)
sprouting helps by
adding a neuronal junction to a damaged NMJ/neuron
myasthenia refers to
muscle weakness
Symptoms of myasthenia Gravis include…
double vision in all directions, see attach pic
By using edrophonium on a person with myasthenia gravis….
symptoms dramatically improve
Mysathenia Gravis and LEMS are
autoimmune diseases which cause the destruction of some acetylcholine channels or calcium channels
A decrease in the sensitivity of the acetylcholine receptors result in
more acetylcholine being released
detubucurarine is a
competitive inhibitor of acetylcholine
to increase the likelihood of acetylcholine channels opening,
increase levels of anticholinesterase
Anticholinesterases prolong
end plate potentials and end plate currents
Omethoate induces µCTX-resistant hypercontractions localised to NMJs
This causes NMJ hypercontractions and are associated with muscle necrosis and synaptic degeneration
Nerve damage triggers
wallerian degeneration
Within 6-15 h of nerve damage.,..
synaptic vesicles are degraded
Within 24 of nerve damage,,,
remnants of terminal has been engulfed by schwann cell
Wallerian degeneration results from activation of
the SARM-1 gene by
a) toxic accumulation of a substrate for the NAD synthetic enzyme NMNAT;
b) depletion of NAD
The WldS gene mutation substitutes for loss of
NMNAT a8er denervation
preventing SARM1 activation
Kranocytes first spread out from NMJs
making contact to axons which still supply NMJ’s
Schwann cells are able to…
form bridges between intact and denervated NMJ’s
Reinnervation is accompanied by
recovery of muscle force
“ALS” comprises a spectrum of syndromes
attach slide pic
90-95 % of ALS cases are
sporadic
Challenges to ALS research includes
prevent motor neurones dying, promote compensation by surviving motor neurons, replace and regenerate lost motor neurones
one potential treatment for ALS could be
Stem cells
In a trial, a mice was rescued from MND,
via SARM 1 inactivation