Muscle Flashcards
Describe the process of muscle innervation
1) action potential arrives at the presynaptic neutron terminal
2) voltage-dependent calcium channels open and Ca2+ ions flow in
3) influx of Ca2+ causes neurotransmitter-containing vesicles to dock and fuse to the presynaptic neuron’s cell membrane resulting in the release of Ach into the synaptic cleft.
4) Acetylcholine diffuses across the synaptic cleft and binds to the nicotinic acetylcholine receptors bound to the motor end plate.
5) postsynaptic receptors are ligand-gated ion channels, and when they bind acetylcholine, they open, allowing sodium ions to flow in and potassium ions to flow out of the muscle’s cytosol causing depolarization of the sarcolemma. This depolarization spreads into the T tubules.
5) Voltage sensor proteins of the T tubule membrane change their conformation
6) Gated Ca2+-release channels of adjacent terminal cisternae are activated by the proteins change in conformation
7) Ca2+ is rapidly released from the terminal cisternae into the sarcoplasm
8) Ca2+ binds to the TnC subunit of troponin causing tropomyosin to move away from actin-myosin binding site
9) The contraction cycle is initiated and Ca2+ is returned to the terminal cisternae of the sarcoplasmic reticulum.
Describe sliding filament theory
1) Attachment: Rigor configuration- myosin head is tightly bound to actin molecule. In death, lack of ATP perpetuates this binding (rigor mortis).
2) Release: ATP binds the myosin head causing it to uncouple from the actin filament.
3) Bending: Hydrolysis of ATP causes the uncoupled myosin head to bend & advance a short distance (5nm)
4) Force Generation: The myosin head binds weakly to the actin filament causing release of inorganic phosphate, which strengthens binding, and causes the ‘power stroke’ in which the myosin head returns to its former position.
5) Reattachment: The myosin head binds tightly again and the cycle can repeat. Individual myosin heads attach and flex at different times causing movement.
What are the key components of muscle, in terms of the sliding filament theory?
Myofibril: A cylindrical organelle running the length of the muscle fibre, containing Actin and Myosin filaments.
Sarcomere: The functional unit of the Myofibril, divided into I, A and H bands.
Actin: A thin, contractile protein filament, containing ‘active’ or ‘binding’ sites.
Myosin: A thick, contractile protein filament, with protusions known as Myosin Heads.
Tropomyosin: An actin-binding protein which regulates muscle contraction.
Troponin: A complex of three proteins, attached to Tropomyosin.
What is the function of purkinje fibres?
- modified monocytes
- rapidly transmit action potentials from the atrioventricular node to the ventricles
What are some features of the purkinje fibres?
- large cells
- abundant glycogen
- sparse myofilaments
- extensive gap junction sites
Describe the histology of cardiac muscle, relating to function
- Striations
- Branching
- Centrally positioned nuclei (1 or 2 per cell)
- Intercalated discs (for electrical & mechanical coupling with adjacent cells)
- Adherens-type junctions (to anchor cells and provide anchorage for actin)
- Gap junctions (for electrical coupling)
- In contrast with skeletal muscle, the T tubules of cardiac muscle are inline with the Z bands and not with the A-I band junction.
Describe the histology of smooth muscle, relating to function
- Cells are spindle-shaped (fusiform) with central nucleus
- Not striated, no sarcomeres, no t tubules
- Contraction still relies on actin-myosin interactions
- Contraction is slower, more sustained and requires less ATP. May remain contracted for hours or days.
- Capable of being stretched
- Responds to stimuli in form of nerve signals, hormones, drugs or local concentrations of blood gases
- Form sheets, bundles or layers containing thousands of cells.
- Thick and thin filaments are arranged diagonally within the cell, spiralling down the long axis like stripes on a barbers pole, so the smooth muscle cell contracts in a twisting way.
Outline the pathophysiology of malignant hyperthermia
- rare, autosomal dominant disorder
- causes a life threatening reaction to certain drugs used for general anaesthesia (volatile anaesthetic agents, and the neuromuscular blocking agent succinylcholine)
- succinylcholine inhibits the action of Ach, acting non-competitively on muscle-type nicotinic receptors. It is degraded by butyrylcholinesterase (much more slowly than the degradation of Ach by acetylcholinesterase)
- in susceptible individuals, these drugs can induce a drastic and uncontrolled increase in skeletal muscle oxidative metabolism, quickly overwhelming the body’s capacity to supply O2, remove CO2 and regulate body metabolism. This eventually leads to circulatory collapse and death if not treated quickly.
- treatment for Malignant Hyperthermia is correction of hyperthermia, acidosis and organ dysfunction, discontinuation of triggering agents and the administration of dantrolene. Dantrolene is a muscle relaxant, which works by preventing the release of calcium.
Outline the pathophysiology of Duchenne’s muscular dystrophy
-Genetic faults causes the absence or reduced synthesis of specific proteins (dystrophin) which anchor the actin filaments to the sarcolemma (cell wall) such that in their absence the muscle fibre cells may tear themselves apart when contracting.
Duchenne muscular dystrophy is the complete absence of dystrophin causing:
- Muscle fibres to tear themselves apart on contraction
- Enzyme creatine (phospho)kinase liberated into serum
- Calcium exits cell causing cell death (necrosis)
- Pseudohypertrophy (swelling) before fat and connective tissue replace muscle fibres
Signs and Symptoms
- Early onset,
- Gower’s sign (use of hands on knees to generate strength)
- Contractures (imbalance between agonist and antagonist muscle)
Treatment
- Steroid therapy (prednisolone)
- Ataluren (PTC124) drug trials in humans; ribosomal interaction to produce dystrophin
Outline the pathophysiology of Myasthenia Gravis
- An autoimmune destruction of the end-plate ACh receptors
- Loss of junctional folds at the end-plate
- A widening of the synaptic cleft
- crisis point is when it affects respiratory muscles
Symptoms presenting are:
- Fatigability and sudden falling due to reduced ACh release
- Drooping eyelids (placing ice on the eyelids decreases acetylcholinesterase activity, therefore treats)
- Double vision
- Effected by general state of health and emotion
Treatment:
-Acetylcholinesterase inhibitors (e.g. neostigmine, physostigmine)
How does botulism affect the neuromuscular junction?
Toxins block ACh release
How does organophosphate poisoning affect the neuromuscular junction?
Irreversibly inhibits acetylcholinesterase, therefore ACh remains in the receptors and muscle stays contracted.
Outline the process of muscle hypertrophy
An increase of muscle mass from work performed against load which leads to more contractile proteins and an increase in fibre diameter.
Metabolic changes include:
- increased enzyme activity for glycolysis
- more mitochondria
- more stored glycogen
- increased blood flow.
Outline the process of disuse muscle atrophy
Maintenance of muscles requires frequent movement against resistance. Without this, muscle fibres don’t die but shrink and weaken (smaller diameter)
Causes:
- bed rest
- limb immobilisation
- sedentary behaviour
- ageing; past the age of 30 muscle mass decreases (50% loss of muscle by 80)
Describe the process of cardiac muscle repair
- incapable of regeneration
- Following damage, fibroblasts invade, divide and lay down scar tissue.
