Skeletal Muscle Contraction & Dysfunction Flashcards
What structures conduct the nerve message?
Voltage gated sodium channels
Which chemicals are released into the synapse?
Acetylcholine
What is the effect of this chemical?
Can the chemical work by itself?
- Doesn’t work by itself
- Uses a nicotinic receptor
What structure does the chemical then enter into?
What’s the next structure the chemical travels into?
- Into T tubules
- Then into the Sarcolemma
What goes on at the thin and thick filaments interactions?
What are the key features of this smooth muscle?
How does cellular excitation lead to shortening?
Name the different parts of a neurone
- Dendrites
- Nerve cell body
- Axon
- Myelin sheath
- Schwann cells
- Nodes of Ranvier
- Axon branch
- Axon terminal
What does the axon contain?
Concentration of ion channels
- Na V
- K V
- Ankyrin
State the different stages of a neuronal action potential graph
- Threshold region: at -55mV
- Depolarisation: From -55mV to 30mV (Sodium conc increases causing influx)
- Repolarisation: From 30mV to -70mV (3Na+ leave &2K+ enter the cell)
- Hyperpolarisation: Goes below the normal region but shoots back up again
Describe the Voltage gated sodium channels
- A family of 9 genes termed SCNA1-9
- Rapid opening upon depolarisation
- Exhibit distinctive inactivation
What does contraction involve?
Contraction involves the interaction of actin & myosin
What is contraction fuelled by?
Fuelled by ATP
What is contraction driven by?
Driven by a rise in [Ca2+]
What events occur during contraction?
Membrane events -> Rise in Calcium -> Binding to sensor ->
Contractile Mechanism (at the same time, ATP is hydrolysed by myosin) -> Myosin interaction -> Cell shortens
Describe the contractile cycle
- Cross bridge formation; release of Pi
- Power stroke: ADP is released, myosin undergoes a conformational change
- ATP binds myosin, causing detachment of myosin from actin; cross bridge dissociates
- ATP hydrolysis occurs, cocking myosin heads
List some factors that could go wrong during the contractile cycle?
- Multiple Sclerosis
- Myaesthesia gravis
- Non-dystrophic myotonias
- Mascular dystrophy
How does the myelin sheath insulate the axon?
- Myelin formation occurs in the peripheral nervous system
- Schwann cells wrap around the axon many times
- Each Schwann cell forms myelin around a small segment of one axon
- The Nodes of ranvier is a section of unmyelinated axon membrane between two Schwann cells
How long is each section of the myelin sheath?
1-1.5 mm
What does the CNS neurones contain in comparison to the PNS neurones?
- CNS = Oligodendrocytes
- PNS = Schwann cells
What is the issue with the myelin sheath?
- Myelin does not allow movement of ions
- Nodes of ranvier contain NaV and Kv channels
- Minimize number of Na/K ATPase required
What happens during Multiple Sclerosis?
- Immune attack of myelin
- Leaky blood brain barrier
- Sclerotic lesions such as:
- Numbness, Tingling, Speech problems, Visual problems
What happens during Myaesthesia Gravis?
- Muscle nicotinic AChRs become degraded
- Is a type of autoimmune disease
- Targets the ã1 subunit
- Neuronal nicotinic AChR’s unaffected
What are some symptoms of Myaesthesia Gravis?
- Muscle weakness
- Drooping eyelids
- Fatigue
- Difficulty swallowing or talking
- Exertion is difficult
What are the features of non dystrophic myotonias?
- Delayed relaxation of the muscle after voluntary contraction or mechanical stimulation
- Electrophysiologically characterised by highly organised repetitive electrical activity of the muscle fibres
What happens during Non dystrophic myotonias?
Five different skeletal muscle disorders are caused by mutations to the SCN4A gene that encodes for a voltage gated sodium channel expressed in the skeletal muscle
What do these mutations result in?
- Decreased rate of channel inactivation
- Increased rate of recovery from inactivation
Or - slower channel deactivation
What do these mutations further lead to?
- Less Cl channel activity
- Prolonged contraction
What is Dystrophic myopathy?
- The dystrophin gene contains 79 exons
- Spans >2,200 kb = 0.1% of the genome
- Located in the short arm of the X chromosome
What are the different types of Dystrophic myopathy?
- Duchenne = Total loss of Dystrophin
- Becker = Reduced or dysfunctional dystrophin
What does Dystrophic myopathy lead to?
- Increased permeability to macromolecules
- Abnormal permeability is made worse by mechanical stress
- Muscle fibre necrosis, fibrosis and fat infiltration
