Session 8 Muscle + Muscle disease Flashcards
Classify three types of muscle
- Skeletal Muscle (striated)
- Cardiac Muscle (striated)
- Smooth Muscle (non-striated)
Describe the Ultrastructure appearance of skeletal muscle and state which bands contain actin, myosin or both
MHAZI - The M line is in the H band, which is in the A band. The Z line is in the I band.
The Thin Filament is Actin.
The Thick filament is Myosin.
What is the structure of actin?
Actin, tropomyosin and troponin molecules form the thin (actin) filaments of skeletal and cardiac muscle.
A troponin complex is attached to each tropomyosin molecule, covering the binding sites for the myosin filament.
What is the structure of myosin?
Each thick (myosin) filament consists of many myosin molecules, whose heads protrude at opposite ends.
How does binding of myosin head to actin binding sites occur?
When increased amounts of ionic calcium bind to TnC of troponin, a conformational change moves tropomyosin away from actin’s binding sites. This displacement allows myosin heads to bind actin, and contraction begins.
Give process of muscle contraction
Stage 1 of contraction – Attachment
Rigor configuration: myosin head is tightly bound to actin molecule. In death, lack of ATP perpetuates this binding (rigor mortis).
Stage 2 of contraction – Release
ATP binds the myosin head causing it to uncouple from the actin filament.
Stage 3 of contraction – Bending
Hydrolysis of ATP causes the uncoupled myosin head to bend & advance a short distance (5nm)
Stage 4 of contraction – 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.
Stage 5 of contraction – Reattachment
The myosin head binds tightly again and the cycle can repeat. Individual myosin heads attach and flex at different times causing movement.
Describe the mechanism of innervation of muscle and excitation contraction coupling
- Upon the arrival of an action potential at the presynaptic neuron terminal, voltage-dependent calcium channels open and Ca2+ ions flow from the extracellular fluid into the presynaptic neuron’s intracellular fluid.
- This influx of Ca2+ causes neurotransmitter-containing vesicles to dock and fuse to the presynaptic neuron’s cell membrane. Fusion of the vesicular membrane with the presynaptic cell membrane results in the release of Ach into the synaptic cleft.
- Acetylcholine diffuses across the synaptic cleft and binds to the nicotinic acetylcholine receptors bound to the motor end plate.
- These 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 – depolarization of the sarcolemma. This depolarization spreads into the T tubules.
- Voltage sensor proteins of the T tubule membrane change their conformation
- Gated Ca2+-release channels of adjacent terminal cisternae are activated by the proteins change in conformation
- Ca2+ is rapidly released from the terminal cisternae into the sarcoplasm
- Ca2+ binds to the TnC subunit of troponin
- The contraction cycle is initiated and Ca2+ is returned to the terminal cisternae of the sarcoplasmic reticulum.
Explain the macrostructure of muscle
Epimysium covers muscle
Many fascicles made up of muscle fibres (cells) within
Perimysium surrounds fascicles
Endomysium surrounds muscle fibres within fascicle
What lies between muscle fibres and collagen bundles in tendons?
Sarcolemma
Explain the hierarchical composition of a typical skeletal muscle outlining the principal components at molecular, organellar, cellular, histological and regional anatomical levels
Typical skeletal muscles are composed of…
Fascicles, which are composed of…
Muscle fibres (cells), which are composed of…
Myofibrils, which are composed of…
Myofilaments – actin and myosin.
Give 6 features of fast twitch muscle fibres
White in colour
Contract very quickly and powerfully (sprinting, eyemovement)
Energy released through anaerobic respiration
Lots of neuromuscular junctions
Few mitochondria
Few myoglobin
Give 6 features of slow twitch muscle fibres
Red in colour
Contract slowly for a long period of time (running, postural muscles)
Energy released through oxidative phosphorylation
Fewer neuromucular junctions
Lots of mitochondria
Lots of myoglobin
Give five features of skeletal muscle
Striated T tubles in line with A-I band junction Multinucleated at periphery of cells Voluntary control Rapid, forceful
Give five features of cardiac muscle
Striations
Branching of muscle fibres
Centrally positioned nuclei (1 or 2 per cell)
Intercalated discs between muscle fibres for electrical and mechanical coupling
Gap junctions (for electrical coupling)
T tubules inline with Z line
Give five features of smooth muscle
Not striated, no sarcomeres, no t tubules
Cells are spindle shaped
Contraction is slower and more sustained
Responds to stimuli in form of never signals, hormones, drugs and blood gasses
Thick and thin filaments arranged diagonally in cell
Capable of being stretched
How can skeletal muscles repair themselves?
- Cells cannot divide
- Hyperplasia following mitotic activity of satellite cells
- Hypertrophy following fusion of satellite cells with existing muscle
- Gross damage repaired by connective tissue
- If nerve or blood supply interrupted, muscle fibres replaced by fibrous tissue
Can cardiac muscle repair themselves? What occurs after damage?
Incapable of regeneration
Following damage, fibroblasts invade, divide and lay down scar tissue.
Can smooth muscles repair itself? Where is this particularly evident?
Cells retain their mitotic activity and can form new smooth muscle cells
This ability is particularly evident in the pregnant uterus where the muscle wall becomes thicker by hypertrophy (swelling) and by hyperplasia (mitosis) of individual cells
What do purkinje fibres do?
transmit action potentials to the ventricles from the atrioventricular node
Describe structure of purkinje fibres
large cells with:
Abundant glycogen
Sparse myofilaments
Extensive gap junction sites
Why are purkinje fibres important?
They conduct action potentials rapidly compared to regular cardiac muscle. This rapid conduction enables the ventricles to contract in a synchronous manner.
How does skeletal muscle remodelling take place?
continual process. The replacement of contractile proteins happens in ~2 weeks…
Destruction > Replacement = Atrophy Replacement > Destruction = Hypertrophy
Give three ways in which atrophy can occur
Disuse atrophy
muscle fibres don’t die but shrink and weaken
Age
past the age of 30 muscle mass decreases
Denervation
atrophy; muscle no longer receives contractile signals that are required to maintain normal size
Give an example of where you can find extremely hypertrophied muscle
Matt’s arms.
What is hypertrophy?
An increase of muscle mass from work performed against load leads to:
More contractile proteins, increase in fibre diameter.
Give three metabolic changes as a result of hypertrophy
Increased enzyme activity for glycolysis, increased mitochondria, increased stored glycogen
Outline what occurs to ACh at neuromuscular junction
ACh is terminated by acetylcholinesterase.
At high motor neuron firing rates, ACh release decreases
(Only 25% of ACh receptors need to be occupied to open the sodium channels on the motor end plate)
What happens in 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
What is the crisis point of myasthenia gravis?
when it affects respiratory muscles
Give four symptoms of Myasthenia Gravis
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
What is a treatment for Myasthenia Gravis/
Acetylcholinesterase inhibitors
How does botulism work?
Toxins block ACh release
What occurs in organophosphate poisoning?
Irreversibly inhibits acetylcholinesterase, therefore ACh remains in the receptors and muscle stays contracted.
What is Duchenne’s muscular dystrophy?
Recessive x-linked condition
Complete absence of dystrophin causing:
- Muscle fibres to tear themselves apart on contraction
- Enzyme creatine (phospho)kinase liberated into serum
- Calcium enters cell causing cell death (necrosis)
- Pseudohypertrophy (swelling) before fat and connective tissue replace muscle fibres
Give two symptoms of duchenne’s
Early onset, Gower’s sign (use of hands on knees to generate strength)
Contractures (imbalance between agonist and antagonist muscle)
Give a treatment for duchenne’s
Steroid therapy (prednisolone)
What is malignant hyperthermia?
autosomal dominant disorder that causes a life threatening reaction to certain drugs used for general anaesthesia.
What does Succinylcholine do in someone with malignant hyperthermia?
Causes uncontrolled increase in skeletal muscle oxidative metabolism, quickly overwhelming the body’s capacity to supply O2, remove CO2 and regulate body metabolism.
Circulatory collapse and death.
How is malignant hperthermia treated?
by the correction of hyperthermia, acidosis and organ dysfunction, discontinuation of triggering agents and the administration of dantrolene.
What does Dantrolene do?
Dantrolene is a muscle relaxant, which works by preventing the release of calcium.
