NMJ Flashcards
What is meant by the NMJ
A specialised synapse between a motor neuron and a muscle fibre.
How does the neuron innervate the muscle fibre
Lots of branches of the motor neuron on the muscle fibre.
When are neuromuscular diseases particularly dangerous
When they affect muscles that keep you alive, for example your diaphragm.
What are motor neurons divided into
Upper and lower, depending on where they go from the brain to the brainstem or the brain to the spinal cord.
How can we take advantage of action potentials clinically
We can take advantage of the flow of charge to record action potentials, when monitoring the activity of muscle fibres at rest and during contraction. This allows us to diagnose disease, differentiate between causes and monitor the progression of the disease.
Describe, basically, synapses
Allows for contact from neuron to muscle or from neuron to neuron.
Basic structure is similar throughout the nervous system.
Arrangements can be simple or complex.
Contact ratio – ranges from 1:1 for muscle to 103:1 in the CNS
In the NMJ what is the synaptic cleft the space between
The motor neuron and the muscle fibres
What is the end of the axon called
The motor end plate, which is relatively large.
Thin axon which enlarges near the muscle fibre.
Where do many neuromuscular problems occur
In the calcium ion channels on the pre-synaptic terminal
What is the key feature of neuromuscular disease
Muscle contraction cannot take place
However, there are many things that can go wrong which all lead to this. Therefore, it is important to determine the cause, to ensure that the appropriate treatment is given.
What are the main structures constituting the NMJ
presynaptic nerve terminal
synaptic cleft
postsynaptic endplate region on the muscle fibre
Describe the structure of the NMJ
A specialized structure incorporating the distal axon terminal and the muscle membrane that allows for the unidirectional chemical communication between peripheral nerve and muscle
What is the neurotransmitter for voluntary striated muscle
Acetylcholine serves as the neurotransmitter for voluntary striated muscle
Where are the cell bodies for motor neurons found in the spinal cord
In the anterior horn of the grey mater,
What does a single muscle fibre receive innervation from
One branch of a single motor neurone.
Initially, during development, received more, but selectively inhibited some to leave one.
Describe the difference between upper and lower motor neurons
Upper- brain stem and brain- where signals for voluntary movement originate
Lower- brainstem- face spinal cord- limbs and trunk
Why is it important clinically that each muscle fibre only receives innervation from one branch
When the nerves are cut, due to trauma, the regrowth of nerves permits the innervation of more than one muscle fibre, different action potentials recorded for injured and uninjured nerve
Nerves sprout and innervate muscle fibres that were previously innervated by other muscle fibres.
Describe how muscle contraction is initiated
The NMJ is responsible for initiating muscle contraction.
Action potential open V-gated Ca2+ channels
Ca2+ enters
Ca2+ triggers exocytosis of vesicles
Acetylcholine diffuses in cleft
Acetylcholine binds to receptor-cation channel & opens channel
Local currents flow from depolarized region and adjacent region; action potential triggered and spreads along surface membrane
Acetylcholine broken down by acetylcholine esterase (enzyme). Muscle fibre response to that molecule of Acetylcholine ceases
Describe the roles of SNAREs in vesicle docking
SNAREs on the vesicle (v-SNAREs) interact with complementary SNAREs on the target membrane (t-SNAREs), firmly docking the vesicle in place
Describe the release of Ach from the NMJ
Released periodically at rest, in discrete amounts (which shows that it is packaged in vesicles), causing upward deflections on the EMG, but the depolarisation is not enough to generate an action potential.
At rest, individual vesicles release ACh at a very low rate causing miniature end-plate potentials (MEPPs)
Set number of molecules in each vesicle (amplitudes are similar)
Describe smooth muscle
Surrounds circular and hollow organs, under involuntary control
What is the muscle made up of
Fascicles which are collections of muscle fibres surrounded by connective tissue, myofibrils within muscle fibres- gives muscle its striated appearance
Describe the myofibres
Covered by plasma membrane – sarcolemma
T-tubules tunnel into centre
Cytoplasm called sarcoplasm – myoglobin and mitochondria present (due to large energy demand)
Network of fluid filled tubules – sarcoplasmic reticulum
Composed of myofibrils
What gives skeletal muscle its striated appearance
The discrete arrangement of proteins within the striated muscle.
Describe the myofibrils
1-2μm in diameter
Extend along entire length of myofibres
Composed of two main types of protein – actin and myosin
When is more force generated
As muscles get longer. Eccentric contractions- where most damage occurs.
Describe myofilaments
Light and dark bands give muscle striated appearance
Do not extend along length of myofibers
Overlap and are arranged in compartments called sarcomeres
What are A and I bands named after
Their effects on polarised light
Dark bands – A band (thick - myosin)
Light bands – I band (thin - actin
What are Z lines, M lines and H bands named after
Location
Dense protein Z-discs separate sarcomeres
Myosin and actin filaments overlap- H zone
Describe the observations of the sliding filament model
During contraction I band became shorter
A-band remained same length- they are pulling the actin over it
H-zone narrowed or disappeared
Describe the activation and relaxation process
Action potential propagates along surface membrane and into T-tubules
DHP (dihydropyridine) receptor in T-tubule membrane: senses V & changes shape of the protein link to Ryanodine receptor, opens the Ryanodine receptor Ca2+ channel in the SR membrane; Ca2+ released from SR into space around the filaments
Ca2+ binds to Troponin & Tropomyosin moves allowing
Crossbridges to attach to actin
Ca2+ is actively transported into the SR continuously while action potentials continue. ATP- driven pump (uptake rate < or = release rate).
Ca2+ dissociates from TN when free Ca2+ declines; TM block prevents new crossbridge attachment; Active force declines due to net crossbridge detachment
What happens in rigor mortis
No energy from ATP to detach myosin from actin
But eventually gets broken down- the muscles become flaccid again.
What happens once the action potential stops
No release of calcium
SR constantly transporting calcium, all gets taken up now
Describe disorders of the NMJ
Pathological processes interfering with NMJ function can cause muscle weakness Examples: Botulism Myasthenia gravis (MG) Lambert-Eaton myastenic syndrome (LEMS)
Describe botulism
Botulinum toxin produces an irreversible disruption in stimulation-induced acetylcholine release by the presynaptic nerve terminal
Paralyses the muscles.
Potentially fatal- especially if diaphragm is paralysed
Describe Myasthenia Gravis
An autoimmune disorder where antibodies are directed against the acetylcholine receptor.
There may be a personal or family history of other autoimmune diseases. It cause fatigable weakness (i.e. becomes more pronounced with repetitive use) and may affect the ocular, bulbar, respiratory or limb muscles.
Antibodies are detected in nearly 90% of cases and EMG examination will confirm the diagnosis.
In severe cases the antibodies in the blood can be removed via plasma exchange which allows rapid improvement to occur.
Why can muscles not contract in myasthenia gravis
No acetylcholine binding to receptors on the postsynaptic terminal. Hence no calcium influx into the muscle- no contraction
What does bulbar relate to
The brainstem
Describe corticospinal and corticobulbar tracts
Corticospinal- cortex to spinal cord- limbs
Corticobulbar- cortex to brainstem- face (eyes, talking, forming expressions)
How can we treat myasthenia gravis
Not all receptors blocked
Inhibit acetylcholinesterase
Keep more Ach in synaptic cleft
More likely to bind to available receptors
Test for this disease, inject this drug, symptoms disappear almost immediately.
What is Myasthenia gravis associated with
Lymphoid hyperplasia and tumours of the thymus. Weakness may respond to surgical thymic removal, especially in young patients with short history. Otherwise treatment is with immunosuppression and anti-cholinesterases (pyridostigmine, neostigmine).
Describe Lambert-Eaton myasthenic syndrome
an autoimmune disease caused by antibodies directed against the voltage-gated calcium channel (VGCC) - associated with lung cancer.
No acetylcholine release, no contraction
How could we treat Lambert-Eaton myasthenic syndrome
Release a compound that mimics acetylcholine
Initially lessened with exercise.
