Lecture 6 NS - NMJ and muscle contraction Flashcards
What is a neuromuscular junction?
A specialised synapse between a motor neuron and a muscle fibre
What is the structure of a synapse?
What is the function of a synapse?
Allows contact from neuron to msucle or vice versa -> ratio is 1:1 for muscle to 10000:1 in the CNS
What is the structure of the NMJ? FITB
The junctional folds increase the SA 3x as there aren’t receptors present all the way into the fold
What is the NMJ structure?
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 are the main structures constituting the NMJ?
Presynaptic nerve terminal, synaptic cleft, postsynaptic endplate region on muscle fibre
What is the neurotransmitter for voluntary striated muscle?
ACh
How is the innervation of muscle organised?
NB: each motor unit has it’s own muscle fibre which has no other innervation
How is muscle contraction initiated in the NMJ?
Action potential open VGCC -> Ca2+ enters and triggers exocytosis of vesicles. ACh diffuses in cleft and binds to receptor-cation channel and opens channel. Local currents flow from depolarized region and adjacent region; AP triggered and spreads along surface membrane. ACh broken down by acetylcholine esterase. Muscle fibre response to that molecule ceases production of ACh
How are minature end-plate potentials formed?
At rest individual vesicles release ACh at very low rate-> reflect balance of Ca2+ intracellular in presynaptic terminal
How is skeletal muscle organised?
Muscle > muscle fibres > myofibril > myofilaments
What is the structure of myofibres?
Covered by sarcolemma with T-tubules tunnel into centre -> sarcoplasm has myoglobin and mitochondria present. Has a network of fluid filled tubules (sarcoplasmic reticulum) and is composed of myofibrils
What are myofibrils?
1-2 micrometres in diameter and extend along entire length of myofibres -> composed of actin and myosin
What are myofilaments?
Light and dark bands give striated appearance. Don’t extend the whole length of myofibres -> overlap and are arranged in sarcomeres
How are myofilaments organised?
Dense protein Z-discs separate sarcomeres, dark A-bands (thick-myosin), thin I-band (thin-actin) which overlap
What is the sliding filament theory?
During contraction I band becomes shorter, A band remains same length and H zone narrows/disappears
What is the process of activation and relaxation in muscles?
AP propagates along surface membrane and into T-tubules, where the DHP receptor senses and changes shape of the protein link to RyR, opens the RyR in the SR membrane. So, Ca2+ released from SR into space around the filaments, where it binds to Troponin/Tropomyosin which moves allowing crossbridges to attach to actin. Ca is actively transported into SR continuously while AP continue. ATP- driven pump (uptake rate
What are disorders of the NMJ?
Pathological processes interfering with NMJ function can cause muscle weakness
What are some examples of disorders of NMJ?
Botulism, myastenia gravis and Lambert-eaton myastenic syndrome
How does botulism work?
Botulinum toxin produces irreversible disuption in stimulation-induced ACh release by presynpathetic nerve terminal
How does myastenia gravis work?
Autoimmune disease caused by Ab against ACh
How does LEMS work?
Associated with lung cancer, but is an autoimmune disease caused by Ab directed against the VGCC
