Advanced Muscle Physiology Flashcards
What is the structure of the muscle?
Fascicle Fibre Myofibril Split into sarcomeres Contains myofilaments Z line is made of alpha actinin
What is the crossbridge theory
The tension generated in a muscle is dependent on the area of overlap- the more overlap, the mote crossbridges, the more tension generated in th muscle
Myosin heads attach to the actin and pull the Z lines towards each other
Sliding myofilament hypothesis
Neuroal action potential Muscle action potential Voltage gated Ca channels open Ca infux Myofilaments slide Contraction
What is the motor unit
Motor unit- this is the motor neuron and all of the muscle fibres innervated by it.
A single motor neuron can innervate a small/large number of fibres, depending on the fine control needed
Muscle have multiple motor units
More motor units- more graded contraction and spatial summation- more fine control over the muscle
What is the NT used in the NMJ
ACh on NAChR
How is the AP in the NMJ mediated
By Nav, repolarisation by Kv, increased membrane potential means Cav open- NT release
Describe the muscle AP
Initial depolarisation- activation of NAChR which takes it to threshold for Nav.
Repolarisation is mediated by Kv channels.
Duration is 1-2m/s
What mediates the closing of the Na channels
The depolarisation- this mediates the opening and the closing of the channels (change configuration to inactive)
The depolarisation also mediates the opening of Kv
Features of the NAChR
Non-selective ligand gated ion channel- Na, K and Ca can move through
Nernst is about 0mV which is half way ish between Na and K
When channel opens- depolarisation
Activation of this alone is not sufficient for AP- mediates the change it potential to open the Nav channels.
4 subunits, Pentameric, 2 binding sites
Both binding sites must be bound to activate
How many NAChR aloha subunit genes are there
9- 1 is found in the muscle
2-8 in the neurons
How many NAChR beta subunit genes are there
4- 1 in skeletal muscle and 2-4 in neuronal
How many vesicles are there in the NMJ
approx 200, each with 6000 to 10000 ACh- don’t need that much vesicel fusion to activate the channel
What is myasthenia gravis?
Most common NMJ disease
Make antibodies against muscle AChR (neuronal types not affected)
Weakness and tiredness of muscles- can be fatal if respiratory muscles fail
What evidence is there that antibodies are to blame for myasthenia gravis?
87% of patients have them against AChR. Non-MG patients don’t
Inject mice with AChR antibodies and they lose the ability to stand up
Treatment for MG
ACh-transferase inhibitors0 enhances ACh Immunosupressants to reduce AB levels Plasmapheresis- remove ABs from blood Corticosteroids IV immunoglobulins- mops up the ABs Thymectamy- remove the thymus so removal of the ACh AB secreting B-cells
