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Flashcards in ToB S10 - Muscle Deck (33)
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Describe the ultrastructure appearance of skeletal muscle


The M line is in the H band, which is in the A band The Z line is in the I band


What is the actin filament made up of in muscle?

Made up of actin, tropomyosin and troponin (3 types)

1) TnI - binds to actin

2) TnC - binds with calcium

3) TnT - binds with tropomyosin


Outline the mechanism of muscle contraction

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 and 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 attach and flex at different times causing movement


Describe the mechanism of innervation of muscle and excitation contraction coupling

1) Action potential arrives at the presynaptic neutron terminal. Voltage-dependent calcium channels open and calcium ions flow from extracellular fluid into the presynaptic neurones intracellular fluid

2) Influx of Calcium ions causes neurotransmitter-containing vesicles to dock and fuse to the presynaptic neurones cell membrane. Fusion of the vesicular membrane with the presynaptic cell membrane results in the release of ACh into the synaptic cleft

3) ACh diffuses across the synaptic cleft and binds to the nicotinic ACh receptors bound to the motor end plate

4) Postsynaptic ligand-gated ion channels open to allow sodium ions to flow in and potassium ions flow out of the muscles cytosol - DEPOLARISATION OF THE SARCOLEMMA. Depolarisation spreads into the T tubules

5) Voltage sensor proteins of the T tubule membrane change their conformation

6) Gated calcium ions release channels of adjacent terminal cisternae are activated by the proteins change in confirmation

7) Calcium ions rapidly released from terminal cisternae into the sarcoplasm

8) Calcium binds to the TnC subunit of troponin

9) The contraction cycle is initiated and calcium ions is returned to the terminal cisternae of the sarcoplasmic reticulum


Describe the connective tissue that surrounds muscle

Epimysium, perimysium and endomysium

Epi - on/above

Peri - Around

Endo - Inside


Explain the hierarchical order of muscle organisation

Typical muscles are composed of.....

Fascicles, which are composed of .....

Muscle fibres (cells), which are composed of .....

Myofibrils, which are composed of ......

Myofilaments made up of actin and myosin.


Describe the limited nature of repair possible in a mature muscle

Skeletal muscle - Cells cannot divide but the tissue can regenerate by mitotic activity of satellite cells, so that hyperplasia follows muscle injury - Satellite cells can fuse with existing muscle cells to increase mass - Gross damage is paired by connective tissue which leaves a scar - If nerve or blood supply is interrupted, muscle fibres replaced by fibrous tissue


Cardiac muscle - Incapable of regeneration - Following damage, fibroblasts invade, divide and lay down scar tissue


Smooth muscle - Cells retain mitotic activity and can form new smooth muscle cells - Particularly evident in pregnant uterus where muscle becomes thicker by hypertrophy (swelling) and by hyperplasia (mitosis) of individual cells


Describe the histology of cardiac muscle

- Cardiac cells are branched cylinders

- mono- or bi- nuclear cells with central nuclei - Contains striations

- Abundant connective tissue with blood vessels

- T-tubules food at the level of the Z disc

- Sarcoplasmic reticulum less extensive than skeletal muscle

- Diads rather than triads - A T-tubule interacting with 1 sarcoplasmic cisternai

- Mitochondria more numerous than in skeletal muscle

- Many blood vessels; reflects aerobic metabolism of tissue

- There are no satellite cells, so regeneration of muscle not possible Intercalated discs with junctional complexes

- Desmosomes, Fasciia adherens, gap junctions - enable ionic communication between cells leading to synchronous muscle contractions


Describe the histology of smooth muscle

- 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

- Capable of being stretched

- May be found in bundles or sheets in the walls of the gut, bile duct, ureters, urinary bladder, respiratory tract uterus and blood vessels


Outline the structure of purkinje fibres

- Abundant glycogen

- Sparse myofilaments

- Extensive gap junction sites


Outline the functions of the purkinje fibres

Tracts of purkinje fibres transmit action potential to the ventricles from the atrioventricular node. They conduct action potentials rapidly compared to regular cardiac muscle. This rapid conduction enables the ventricles to contract in a synchronous manner


Describe disuse atrophy

- Maintenance of muscles requires frequent movement against resistance, without this muscle fibres shrink and weaken (don't die) Eg bed rest, limb immobilisation, sedentary behaviour


Describe denervation atrophy

- Muscle no longer receives contractile signals that are required to maintain normal size

- Fasciculation sometimes present (spontaneous twitching of small groups of muscle fibres) If innervation isn't re-established within 3-months there's very poor recovery (completely lost after 2 years)


Outline hypertrophy

An increase of muscle mass from work performed against load leading to:

- More contractile proteins, increase in fibre diameter

- Metabolic changes include increased enzyme activity for glycolysis, increased mitochondrial activity and increased stored glycogen


How is acetylcholine removed from the synaptic cleft and where does it go?

Acetylcholinesterase breaks down acetylcholine in the synaptic cleft. Acteyl and choline produced are reabsorbed by the pre-synaptic neurone to make more neurotransmitter


Outline Myasthenia Gravis

- Autoimmune destruction of end-plate ACh receptors

- Loss of junctional folds at the end-plate

- A widening of the synaptic cleft

The crisis point is when it affects respiratory muscles

Symptoms are:

- Fatiguability and sudden falling due to ACh release

- Drooping eyelids; ptosis - places ice on eyelids to reduce acetylcholinesterase activity

- Double vision

- Effected general state of health and emotion Treatment

- Acetylcholinesterase inhibitors Eg neostigmine, physostigmine


How does Botulism poison the neuromuscular junction?

Block ACh release


How does organophosphate poisoning?

Irreversibly inhibits acetylcholinesterase, therefore ACh remains in the receptors and muscle stays contracted


What is a sarcomere?

Distance between m lines or z bands, a unit of muscle


List 5 differences between red and white cells in skeletal muscle

Red - Slower contraction, rich in myoglobin, smaller diameter, rich blood supply, rich in oxidative enzyme, numerous mitochondria

White - Faster concentration, larger diameter, few oxidative enzymes, poor blood supply, more neuromuscular junctions


Describe the role of calcium in the sliding filament mechanism?

Calcium is released from the sarcoplasmic reticulum when stimulated by an action potential carried by the T tubules. Calcium ions bind to the TnC unit on the troponin complex and cause a conformational change of the tropomyosin molecule that exposes the actin binding site. The myosin head can then attach and the process of muscle contraction begins. Calcium ions are then reabsorbed by active transport back into the sarcoplasmic reticulum.


Outline the changes that occur in a sarcomere during muscle contraction

A band stays the same length I-band shortens H-zone shortens Z-lines move closer together


Name the five steps of muscle contraction (simple)

1) Attachment

2) Release

3) Bending

4) Force generation

5) Reattachment


What is the name given to the region connecting the muscle and tendon?

Myotendinous junction


Describe the development of skeletal muscle

Myogenic stem cells differentiate to form myoblasts

Myoblasts fuse to form primary myotube

Nuclei are displaced to the periphery by newly synthesised actin and myosin


What is unique about smooth muscle and its mechanism of repair compared to cardiac and skeletal muscle?

Retains its mitotic ability so can regenerate itself


What are the three causes of atrophy?

Disuse- muscles require frequent movement against resistance to prevent weakening

Denervation- muscles no longer receive contractile signals required to maintain normal size

Aging- past age of 30 muscle mass decreases, 50% lost by 80


What is the cause of Duchenne Muscular Dystrophy?

X linked genetic disease which results in the complete absence of dystrophin


Which is succinylcholine and what does it cause?

Neuromuscular blocking agent Causes Malignant Hyperthermia whereby succinylcholine molecules prevent the binding of acetylcholine to end plate receptors by non-competitive inhibition


Outline the pathophysiology of muscular dystrophy

Genetic faults causes the absence or reduced synthesis of DYSTROPHIN, which anchor the actin filaments to the sarcolemma such that in their absence the muscle fibre cells may tear themselves apart when contracting