6. NMJ and muscle contraction Flashcards
Neuromuscular junction (NMJ)
A specialised synapse between a motor neurone and a muscle fibre
Synapse
“contact or junction”
Allows for contact from neurone to muscle or from neurone to neurone.
Can be simple or complex.
Contact ratio: ranges from 1:1 for muscle to 10^3:1 in CNS
What is the enlargement at the end of an axon pre-NMJ called?
Motor end plate
What is the neurotransmitter for voluntary striated muscle?
Acetylcholine (ACh)
How are motor neurones organised?
Into upper (in brain) and lower (in brain stem to face or spinal cord if to muscles in arms/legs)
What innervation is received by a single muscle fibre?
Innervation from 1 branch of 1 motor neurone
What may injury allow in terms of re-innervation?
Re-innervation of muscle that has previously been innervated by other neurones
Describe what occurs when an AP reaches the NMJ
- AP opens VGCC
- Ca2+ enters and triggers exocytosis of vesicles
- ACh diffuses in cleft
- ACh binds to receptor-cation channel and opens channel
- Local currents flow from depolarized region to adjacent region; AP triggered and spreads along surface membrane
- ACh broken down by acetylcholine esterase (enzyme). Muscle fibre response to that molecule of ACh ceases
Miniature end-plate potentials (MEPPs)
At rest, individual vesicles release ACh at a very low rate causing miniature end-plate potentials (MEPPs)
=Occasional upward deflections on graph (don’t result in muscle contraction)
Skeletal muscle structure
Muscle attached to skeleton
Voluntary contraction
Made of fascicules (collection of muscle fibres surrounded by connective tissue)
Striated
Describe the structure of myofibres
Covered by plasma membrane: sarcolemma
T-tubules tunnel into centre
Cytoplasm called sarcoplasm (myoglobin and mitochondria present)
Network of fluid filled tubules: sarcoplasmic reticulum
Composed of myofibrils
Describe the structure of myofibrils
1-2μm in diameter
Extend along entire length of myofibres
Composed of Actin and Myosin
What are the 2 subtypes of isotonic contraction?
Concentric: shortening
Eccentric: lengthening
Describe the structure of myofilaments
Light and dark bands give muscle striated appearance
Do not extend along length of myofibers
Overlap and are arranged in compartments called sarcomeres (Z disc to Z disc)
What makes up the striated appearance of myofibrils
Dark bands: A band, thick: myosin
Light bands: I band, thin: actin
What observations can be made during muscle contraction?
I band became shorter
A-band remains same length
H-zone narrows/ disappears
Describe the process of excitation-contraction coupling of skeletal muscle
An AP propagates along sarcolemma and T tubules
Reaches the Dihydropyridine receptors
Depolarisation causes a conformational change in the DHPRs
Change transmitted to Ryanodine Receptors on sarcoplasmic reticulum
RyR opens: causing Ca2+ release from intracellular stores
Ca2+ binds to Troponin and Tropomyosin moves, allowing cross bridges to attach to actin
Ca2+ actively transported into SR continuously throughout
Ca2+ dissociated from troponin when free Ca2+ declines, Tropomyosin prevents new cross bridge attachment
Active force declines due to net cross bridge detachment
3 examples of diseases where pathological processes interfere with NMJ function
Botulism
Myasthenia gravis (MG)
Lambert-Eaton myastenic syndrome (LEMS)
Botulism
Botulinum toxin produces an irreversible disruption in stimulation-induced ACh release by the presynaptic nerve terminal
(Stops release of ACh into synapse)
Can cause paralysis of muscles
Myasthenia Gravis
An autoimmune disorder where antibodies are directed against the ACh receptor
Receptor no longer receptive to ACh, so can’t contract
Signs and symptoms of Myasthenia Gravis
Personal/ family history of autoimmune diseases
Fatigable weakness
May affect ocular, bulbar, respiratory or limb muscles
What can give Myasthenia Gravis the potential to be treated?
Not all receptors are blocked, so if ACh is kept in synapse longer (Not broken down by ACh esterase) muscles will respond
In severe cases the antibodies in the blood can be removed via plasma exchange which allows rapid improvement to occur.
Lambert-Eaton myasthenic syndrome
An autoimmune disease caused by antibodies directed against the VGCC’s in presynaptic terminals
Ca2+ can’t enter
Associated with lung cancer
Corticospinal track
Cortex + Spinal cords: signals to limbs
Corticobulbar track
Cortex + Bulbar: signals to face muscles
