Skeletal Muscle Flashcards

1
Q

Describe skeletal muscle fibres

A

long, cylindrical multinucleated cells ranging in length from a few mm to 10cm or more.

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2
Q

Describe the layers of skeletal muscle organisation

A

Sarcomere > Myofibrils > Muscle Fibres > Endomysium > Fascicle > Perimysium > Muscle > Epimysium

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3
Q

Where does muscle connective tissue originate?

A

The connective tissue matrix of the muscle is secreted by fibroblasts that lie inbetween muscle fibres. It contains collagen and elastic fibres that merge with the connective tissue of the tendons

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4
Q

What’s the diameter of a myofibril?

A

About 1 micrometer

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5
Q

What’s the rough length of a sarcomere?

A

The fundamental contractile unit is about 2 micrometers long

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6
Q

What is the M line?

A

At the very centre of the sarcomere is the M line where links are formed between adjacent myosin filaments.

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7
Q

What is the H zone?

A

A pale region at the centre of the sarcomere where myosin filaments don’t overlap with actin (when relaxed)

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8
Q

What is the A band?

A

The anisotropic band, which refracts polarised light, includes the extent of the myosin filaments, both in the H zone and where they overlap with actin filaments. This band doesn’t change length during contraction.

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9
Q

What is the I band?

A

The isotropic band doesn’t refract polarised light. It is the the region straddling every Z line, and on either end of each sarcomere, consisting only of actin filaments. Changes length during contraction.

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10
Q

What is the Z line?

A

At either side of the sarcomere, filamentous actin is stabilised by binding to the actinin in the Z line, which aligns with adjacent Z lines by binding with desmin.

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11
Q

Describe the sarcolemma

A

The cell membrane of the muscle fibre. Folded at resting length with indentations called caveolae to allow stretch.

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12
Q

What are T-tubules?

A

Transverse tubules run from the sarcolemma across the junction of the A and I bands. These meet the sarcoplasmic reticulum at terminal cisternae.

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13
Q

What is a triad?

A

A triad describes the complex in which each T-tubule comes into contact with the cisternae of two regions of SR.

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14
Q

What is a motor unit?

A

Collectively describes one motor neuron and all the muscle fibres it innervates.

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15
Q

What is the Neuromuscular Junction?

A

The NMJ refers to the axon terminal, synaptic cleft, and motor endplate of the muscle fiber, where a motor neuron and muscle fibre meet at a synapse.

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16
Q

Describe how motor neurons depolarise the sarcolemma

A

An action potential invades and depolarises the axon terminal of the motor neurone, voltage-gated Ca2+ ion channels in the terminal membrane open and ions flow in, triggering the fusion of docked synaptic vesicles, releasing ACh into the cleft, these bind to nicotinic receptors on the post-synaptic membrane, cation channels open, depolarising the endplate region of the membrane - epp, when this exceeds threshold, the sarcolemma generates an action potential which propogates along the whole fibre.

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17
Q

What is a miniature endplate potential?

A

mepps are small, spontaneous depolarisations of the end-plate region of the sarcolemma. It’s thought that these correspond to the release of a single vesicle of ACh. Frequency increases when the nerve terminal is artificially depolarised.

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18
Q

Why does ACh only act for a few ms?

A

Acetylcholinesterase in the synaptic cleft breaks it down into actetate and choline which can be taken up by the nerve terminal and recycled.

19
Q

What does eserine do?

A

It inhibits the action of Acetylcholinesterase, causing continuous depolarisation of the sarcolemma and blocking neuromuscular transmission

20
Q

What is curare?

A

An arrow poison used for hunting by native South Americans, acts as a neuromuscular blocker that blocks nicotinic receptors

21
Q

Why are nicotinic receptors suited for the NMJ?

A

The ACh binding site is part of the same molecular complex as the Cation channel, so binding directly opens the channel with no intervening step - quicker.

22
Q

What is denervation supersensitivity?

A

When the motor nerve is cut, the terminal degenerates and the endplate loses sensitivity to Ach, while the muscle weakens and atrophies. Following this, the non-junctional sarcolemma becomes sensitive to Ach - trophic action of the nerve.

23
Q

Describe myasthenia gravis

A

Patients make antibodies that bind their own nicotinic receptors, causing functional denervation of muscle. This causes (especially cranial) muscle weakness as no. active receptors declines and NM transmission progressively fails.

24
Q

How can myasthenia gravis be treated?

A

Inhibitors of acetylcholinesterase such as neostigmine prolong activity of Ach

25
How does depolarisation of the sarcolemma increase Ca2+ conc. in the sarcoplasm?
Depolarisation of the sarcolemma spreads along the T-tubules, where voltage sensitive L-type Ca2+ channels on their membrane are linked to ryanodine receptors on the SR, which open due to conformational shape change of L-type Ca2+ channels.
26
What is the role of SERCA?
sarcoendoplasmic reticulum calcium ATPase pumps Ca2+ in the sarcoplasm back into the sarcoplasmic reticulum when nerve stimulation to the muscle stops
27
Describe Myosin and thick filament structure
Each individual molecule has two globular heads and a long thin tail. tail regions associate together to form the thick filaments while the heads stick out to form cross bridges with the thin filaments.
28
Describe thin filament structure
Consists principally of actin, alongside troponin and tropomyosin. Actin molecules link to form one long polymer chain, in which each actin molecule can bind one globular myosin head.
29
What is the effect of sarcoplasmic Ca2+ on the thin filaments?
In its absence, tropomyosin blocks the actin-myosin binding site on the actin molecule. Ca2+ binding troponin causes a conformation shape change that shifts the troponin-tropomyosin complex and exposes the actin binding site.
30
Describe the steps of cross-bridge cycling
ATP bind to the myosin head, breaking the cross-bridge. ATPase: ATP to ADP and Pi, which remain attached to myosin. The myosin head rotates to a "cocked" position to align with another binding site. Then Pi dissociates from the head allowing myosin to bind to actin and causing the powerstroke. ADP dissociates from myosin and myosin awaits another ATP molecule
31
How is contractile force modulated?
Contraction lasts much longer than an action potential. If second action potential occurs before relaxation, cytosolic calcium levels are elevated even more, and contraction force increases.
32
What are the types of summation?
Single twitch, Wave summation, unfused and fused tetanus, where there is no time for contractile force to decrease between action potentials.
33
How come muscle contraction is smooth?
Different Myosin-actin cross-bridges are formed at different times, out of sync, so power strokes are constantly occurring. Asynchronous activation of motor units also plays a role.
34
What are the conditions for maximum muscle power?
An unloaded muscle contracts fastest, but an isometric contraction is able to produce the greatest force. As power = F*velocity of contraction, power is greatest when a loaded muscle contracts at about 1/3 maximal velocity.
35
Isotonic vs Isometric contraction?
No joint movement or change in muscle length in isotonic contraction. Used in rehab as muscle tension is constant.
36
Concentric vs Eccentric Isotonic contraction?
Muscle shortening vs lengthening. In concentric, tension on the muscle increases as it shortens.
37
Factors affecting force of contraction?
- number of active motor units - Cross-sectional area of muscle - frequency of stimulation of motor units - initial resting muscle length - rate of muscle shortening
38
What is Lambert-Eaton Syndrome?
defective release of Ach from motor nerve endings.
39
What endocrine issues can cause myopathy?
Cushing's syndrome and thyrotoxicosis, high levels of corticosteroids and thyroid hormone respectively.
40
What causes Duchenne muscular dystrophy?
A genetic disorder where the gene for dystrophin is faulty or missing.
41
Describe myotonias?
Myopathies causing sustained contraction and slow relaxation. Myotonic dystrophy, caused by an abnormal trinucleotide repeat in a protein kinase, causes weakness of the distal muscles.
42
What are channelopathies?
Defects in ion channels, including hypo and hyperkalaemic periodic paralysis, caused by mutations affecting L-type calcium channels and voltage gated sodium channels respectively.
43
What's McArdle disease?
glycogen storage disease, defect in muscle phosphorylase.
44
What's malignant hyperpyrexia?
administration of anaesthetics triggers muscle rigidity and elevated body temperature, caused by defect in ryanodine receptor.