NMJ Flashcards
What is the NMJ?
specialised synapse between motor neurone (distal axons terminal) and muscle fibre membrane
allows for unidirectional chemical communication between peripheral nerve and muscle
main structures: presynaptic terminal, synaptic cleft, postsynaptic endplate region on muscle fibre
What is the bouton?
presynaptic terminal
What two structures can be found on muscle membrane?
ACh receptor
AChesterase (breakdown neurotransmitter)
What is the main NT for voluntary striated muscle?
ACh
What are the upper and lower motor neurones?
upper - originate in brain
lower - in brain stem to face
in spinal cord to arms, leg or trunk
What emerges through anterior and dorsal/posterior roots of spinal cord?
dorsal root - afferent/sensory neurones
anterior - efferent/motor neurones
What is located in the anterior horn?
efferent neurone cell bodies
Describe the important organisation of motor innervation of muscle fibres?
mixture of nerve fibres innervating mixture of muscle fibres
single muscle fibre only received innervation from branch of one neurone
injury - regrowth of nerve causes innervation from different nerves
Describe NMJ process?
- AP opens VGCCs causing Ca influx to motor end plate
- Stimulates exocytosis of vesicles
- ACh diffuses in cleft and binds to receptor-cation channel to open channel
- local currents flow from depolarised region and adjacent region to spread across muscle surface membrane
- ACh broken down the AChesterase
- Muscle fibre response to ACh stops
What are MEPPs?
at rest vesicles release ACh at very low rate causing miniature end-plate potentials
What is muscle made up of?
Fasciculi of muscle fibres surrounded by connective tissue
What is a myofibre?
covered by sarcolemma and made of myofibrils
T tubules tunnel into sarcoplasm to activate individual proteins (contains mitochondria and myoglobin)
network of fluid filled tubules (SR)
What are myofibrils?
1-2 micrometre diameter
extend along myofibres
made of actin and myosin
striated
What generates more force?
lengthening of muscle fibre
Concentric and eccentric muscle contraction?
Concentric - shorten, thereby generating force
Eccentric - elongate in response to a greater opposing force
What separated sarcomeres?
Z discs
What is the dark band?
A band
thick myosin filament
What is the light band?
I band
think actin filament
How are A and I bands named?
effect on polarised light
What changes and stay same in contraction?
distance between Z discs decreases
A band same length
H zone narrowed/dissappeared
I band shorter
What is the function of the invaginations down into muscle?
- AP propagates along surface membrane into T tubules
- DHP receptor in membrane senses voltage change and changes shape to link to RyR and open Ca channel on SR membrane
- Ca released into sarcoplasm
- Ca binds to troponin and tropomyosin moved so crossbridges attach to actin
- Ca actively transported back to SR continuously while AP continue but ATP
- Ca dissociates from troponin when free Ca declines (no more released from SR) and tropomyosin prevents new crossbridge attachment - ACTIVE FORCE DECREASE DUE TO NET CROSSBRIDGE DETACHMENT
What is the consequence of NMJ function affecting disorders?
cause muscle weakness
What is botulinum toxin?
BOTULISM
causes irreversible disruption in stimulation-induced ACh release by PreS nerve terminal
no muscle effect
What is myasthenia gravis?
autoimmune disorder - antibodies directed against ACh receptor
hereditary?
cause fatigable weakness (more pronounced with repetition), droop eyelids, cannot have face expression easily
ocular/bulbar (corticobulbar tract from cortex to brainstem to face muscles)/resp/limb muscle effects
EMG exam confirms diagnosis. presence of antibodies
remove antibodies in blood via plasma exchange to allow rapid improvement
prevent ACh degradation in synapse
What is Lambert-Eaton myastenic syndrome?
autoimmune disease - antibodies directed against VGCC
failure of transmission at presynaptic site
administer ACh supplement
associated with lung cancer increased risk
What is the function of SNARE protein?
mediate vesicle fusion, that is, the fusion of vesicles with their target membrane bound compartments (such as a lysosome)
