Muscles Flashcards
1
Q
What are the three classifications of muscle?
A
- Skeletal (involved in movement & generation of heat)
- Cardiac
- Smooth
Skeletal and cardiac muscle are striated
2
Q
What does the Latin term ‘Fascis’ mean?
A
Bundle, meaning ~ ‘strength through unity’
3
Q
What are the main structural components of a sarcomere?
A
- Z-line = dark line between 2 sarcomeres
- A-band
- M-line = central line
- I-band = straddles across 2 sarcomeres
- H-Zone = light zone
4
Q
What type of proteins does myosin belong to?
A
A highly diverse family of motor proteins
5
Q
How many different kinds of myosin II are present in various muscle types?
A
9 different kinds
- 8 skeletal/cardiac
- 1 smooth
6
Q
What type of myosin is found in muscle tissue?
A
Muscle myosin is myosin class II
7
Q
What is the role of the myosin head in muscle contraction?
A
It has ATPase activity powered by hydrolysis of ATP
Motor is powered by hydrolysis of ATP
8
Q
What are the two forms of actin?
A
Actin is a major component of eukaryotic cytoskeletons
* G Actin = globular form
* F Actin = filamentous form (FOUND IN MUSCLE)
9
Q
What proteins regulate muscle contraction?
A
- Tropomyosin —> runs along the actin chain (1 tropomyosin for every 7 actin monomers) & consists of 2 alpha helical proteins that are coiled together
- Troponin T —> associates with tropomyosin
- Troponin C —> binds calcium
- Troponin I —> associates with actin and inhibits binding of myosin
- The 3 protein complex (T,C and I) allows contraction of muscle to be regulated by Ca2+
10
Q
What is the function of the neuromuscular junction (NMJ)?
A
To facilitate excitation-contraction coupling
11
Q
What does the T tubule do in muscle cells?
A
Facilitates the spread of action potentials into the interior of the muscle
12
Q
What triggers the release of calcium ions from the sarcoplasmic reticulum?
A
Activation of the DHP receptor
13
Q
What is the sequence of events that leads to muscle contraction?
A
- Acetylcholine released by motor neurone
- Activates nACh receptors
- Sarcolemma depolarised
- Action potential triggered & spreads to T tubules
- DHP receptor activated & triggers ryanodine receptor
- Calcium ions released from sarcoplasmic reticulum
- Troponin C binds Ca2+ and is activated
- Muscle contraction initiated
- Calcium ions pumped back into the SR
14
Q
What happens to calcium ions after muscle contraction?
A
They are pumped back into the sarcoplasmic reticulum
15
Q
What are the three main effects of myasthenia gravis on muscle function?
A
- Receptors become internalized
- Destruction and simplification of the end plate
- Block of the acetylcholine binding sites
16
Q
Fill in the blank: The muscle contraction is regulated by _______.
A
[Tropomyosin and Troponin proteins]
17
Q
True or False: Smooth muscle is striated.
A
False
18
Q
Skeletal muscle structure (8 marks)
A
19
Q
Structure of skeletal muscle fibre
A
- Terminal cisterna
- Triad
- Sarcoplasmic reticulum
- These interact and are involved in excitation of muscle to its contraction
- Sarcolemma (has large SA)
- T tubule (lead from sarcolemma into the interior of the muscle)
20
Q
What composes the striations in the sarcomeres?
A
- Z line connects filament protein types
- M line connects the thicker protein filaments
- Thicker filament is composed of myosin (where the head is closest to the Z line) and titin = seen in H zone
- Titin is the largest protein in the human genome and has a spring-like function = enables muscles to return to their resting state after being stretched
- Thinner filament is composed of actin and nebulin = seen in the I band
- Mixture of both filaments seen in the A band
21
Q
Structure of myosin
A
- Hexamer formed from 2 heavy chains = forms alpha helical tail
- 4 light chains associated with the necks of the heavy chains
- 2x regulatory light chains = regulate activity of myosin heavy chain head groups (important in regulation of smooth muscle)
- 2x essential light chains = mostly structural
- Myosin heads = form interactions with actin.
22
Q
How do actin and myosin trigger muscle contraction?
A
- Myosin head binds to actin chain
- Myosin head binds ATP, causing dissociation of the bond between actin and myosin
- Myosin hydrolyses ATP. ADP + Pi remain bound to myosin head causing a conformation change resulting in the head tilting and entering a ‘cocked’ state
- A weak bond is formed between actin and the myosin head, these are now interacting in a different position = myosin head has moved along the actin chain
- Pi dissociates causing a much stronger bond between actin & myosin = myosin head has returned to its starting position, moving the filaments
- ADP dissociates and myosin is now back in its starting state = muscle has contracted
23
Q
What is the role of troponin I ?
A
- Inhibits formation of cross bridges
- By binding to actin & holding the complex in a position that covers up the binding sites for myosin on the actin chain
24
Q
How is muscle contraction regulated?
A
- When the muscle contracts, there is a rise in Ca2+ concentration in the cytoplasm
- Ca2+ can now bind to troponin C
- This causes a conformation change in the troponin complex
- It shifts on the actin, pulling the troponin further into the actin groove & uncovering the myosin binding sites on the actin chain
- Cross bridges can now form and the muscle can contract
25
Structure of T tubules
- Sarcoplasmic reticulum = associates with the T tubules
- Terminal cisternae = 2 for each T tubule
- Triad
26
How does calcium enter the Sarcoplasmic reticulum?
- High concentration of calcium ions outside the cytoplasm
- VSCC (L-type calcium channel) also known as DHP allows entry of Ca2+ into the cytoplasm
- SERCA = a calcium pump (uses ATP) allows calcium entry into the Sarcoplasmic reticulum
27
How is the T tubule involved in Ca2+ entry?
- DHP in the T tubule is initially in a closed state
- Ryanodine receptor = a calcium channel which has a physical linkage to the Ca2+ channels in the membrane of Sarcoplasmic reticulum
- A change in conformation of DHP is transmitted through the physical linkage to the ryanodine receptor
- Ryanodine receptor will open its channel and Ca2+ can flood out of the Sarcoplasmic reticulum and into the cytoplasm
28
Structure of the DHP receptor
- DHP receptor on the T tubule membrane (4 for each Ryanodine receptor)
- Sarcoplasmic reticulum membrane
- Ryanodine receptor under the SR membrane
29
How is calcium concentration restored in the cytoplasm?
Via the SERCA pump
Pumps Ca2+ from the cytoplasm back into the SR = restores balance and muscle relaxes
30
What is myasthenia gravis?
- Disorder where there is an autoimmune attack on skeletal muscle
- Attacks nicotine receptors (triggers muscle contraction) on muscle membrane
- Leads to muscle weakness and fatigue (as muscles involved in respiration are skeletal muscles) e.g. face drooping, slurred speech
- Can be fatal but effective treatments exist
- Occurs in every 2 out of 10,000 people - more common in women (2x more likely) and most common at ages 20-40 years
- Cause unknown
- May be linked to thymus gland
31
Treatments of myasthenia gravis
- Number of nAChRs greatly reduced
- Use of reversible AChE inhibitors stops breakdown of AChE = increases concentration of ACh in the synapse
- Immunosuppressants —> suppresses immune system BUT this increases risk of catching infections & cancer
- Plasma therapy —> removes autoantibodies from the circulation
32
What happens to the nicotine receptors in myasthenia gravis?
- Typically, Na+ floods into the cell and ACh binds to the receptor located primarily in the alpha subunits (2 binding sites for ACh) and channels open
- In myasthenia gravis, there are antibodies against a specific region of the alpha subunits (near the top of the subunits) known as the main immunogenic region
- These antibodies bind to the alpha subunits resulting in one of 3 things
33
What happens when receptors become internalised in myasthenia gravis?
1. When antibody binds, the cell recognises something is wrong with the receptor and endocytosis occurs
2. Once receptor is inside, it is broken down to amino acids and recycled into new proteins
34
What happens when the end plate is destroyed and simplified in myasthenia gravis?
1. End plate = portion of the muscle membrane under the nerve terminal
2. Infoldings maximise the surface area, receptors are located at the top of the folds
3. When antibodies attach, the immune system will recognise the receptors as something they need to attack leading to an attack of the muscle
4. This results in a dramatic change in structure of the end plate —> it is simplified and folds are lost = nicotine receptors are lost
5. Also results in widening of the synapse
35
What happens there is a block of the ACh binding sites in myasthenia gravis?
Antibodies act as competitive inhibitors = located against the ACh agonist binding sites
36
What is the difference between action potential and contraction time in muscle?
Neurone action potential: 2 ms
Muscle action potential: 20-100 ms (allows force to be maintained without having to fire APs continuously)
Muscle force: varies
37
What are the types of muscle contractions?
Twitch and Tetanus
Twitch = a single action potential
Summation & unfused tetanus = increased rate of APs allows Ca2+ concentrations to reach much higher levels than with a single twitch (this is proportional to muscle force)
Fused tetanus = higher rates of APs where twitches merge into a smooth contraction (maximally stimulated)
38
What is Henneman’s Size Principle?
Stimulus size affects contraction force
As a muscle is stimulated to contract by a neuron in the CNS, motor units will recruit in order of size (smaller ones depolarise first and larger ones will innervate many motor fibres)
39
What are the types of skeletal muscle fibers?
Slow-twitch oxidative, Fast-twitch glycolytic, Fast-twitch oxidative
40
What are the characteristics of slow fibers (Type I)?
Used for posture maintenance, have myoglobin as an oxygen store, many mitochondria
These are resistant to fatigue
41
What are the characteristics of fast-twitch glycolytic fibers (Type IIb)?
Glycolytic fibres
Lactate accumulation & acidosis can limit contraction
Fatigue very quickly
42
What are the characteristics of fast-twitch oxidative fibers (Type IIa)?
Lots of mitochondria, good blood supply, good glycogen stores, resist fatigue
43
Fill in the blank: Type I fibers are primarily _______.
oxidative
44
Fill in the blank: Type IIb fibers are primarily _______.
glycolytic
45
What is the main differences between cardiac muscle and skeletal muscle?
Broadly similar to skeletal muscle = sliding filament mechanism
Differences:
- Branched syncytium (series of fused cells)
- Cells incompletely fused
- Joined by intercalated discs (only found in cardiac muscle)
- Control mechanisms, excitation-contraction coupling & action potentials are different
- Only found in the heart
46
What initiates contraction in cardiac muscle?
SA node action potential
Pacemaker potential = slow depolarisation of the membrane and when brought to threshold, the SA node will fire an AP which will spread through the atria
This is myogenic (originates from within the muscle itself)
47
What is the primary source of calcium in cardiac muscle?
80-90% from sarcoplasmic reticulum via CICR
10-20% Ca2+ current from outside
48
What does the Frank-Starling Law of the Heart state?
Force of contraction is determined by the degree of stretch of cardiac muscle
The more blood returned to the heart, the more the cardiac muscle is stretched
49
What type of metabolism does cardiac muscle primarily use?
Oxidative metabolism
Can’t use glycolytic ATP production as the heart needs to beat continuously
Deprivation of oxygen = angina or heart attack
50
What distinguishes smooth muscle histologically from skeletal and cardiac muscle?
No striations, no t-tubules, spindle-shaped cells
Cells often electrically coupled by gap junctions (unitary - acts as syncytium) but can be independent (multiunit)
51
What is the function of smooth muscle?
Propel contents, regulate flow of substances
Controlled by ANS
52
What are the two types of smooth muscle contraction?
Unitary (syncytium) and Multiunit
53
What is the role of calcium in smooth muscle contraction?
Essential for actin-myosin cross bridges, not involving troponin
54
Fill in the blank: Some smooth muscles have _______ activity.
pacemaker-like
55
What are the key differences in excitation-contraction coupling between muscle types?
Smooth muscle doesn’t involve troponin
Not all smooth muscle requires an action potential to contract
Source of calcium in smooth muscle is extracellular & from the Sarcoplasmic reticulum
56
What type of muscle has a gap junction?
Smooth muscle and cardiac muscle
57
True or False: Cardiac muscle can use glycolytic ATP production.
False
58
How does the autonomic nervous system affect cardiac muscle contraction?
Sympathetic activation increases force, parasympathetic activation decreases force
59
What are the characteristics of fast-twitch oxidative fibers (Type IIa)?
Lots of mitochondria, pretty good blood supply (high myoglobin), good glycogen stores
Resist fatigue
60
What are the characteristics of fast-twitch fibers (Type IIa & IIb)?
Both have fast myosin isoform
Fast Ca2+ transient (high SERCA pump)
Allows rapid shortening but at high energy cost as ATP is hydrolysed quickly
61
What are the properties of different fibre types?
**Slow twitch**
- Red
- Oxidative
- Low myosin ATPase
- High in mitochondria
- Very high number of capillaries
- Low glycogen
- Very high in myoglobin
- Don’t fatigue (low)
- Small diameter
- Low force
**Fast twitch oxidative**
- Red
- Oxidative
- High myosin ATPase
- High in mitochondria
- High number of capillaries
- High in glycogen
- High in myoglobin
- Medium fatiguability
- Medium diameter
- Intermediate force
**Fast twitch glycolytic**
- White
- Glycolytic
- High myosin ATPase
- Low in mitochondria
- Low number of capillaries
- Very high in glycogen
- Low in myoglobin
- High fatiguability
- Large diameter
- High force
62
What is Duchenne muscular dystrophy?
- X linked disorder = disorder in dystrophin gene
- affects 1:3500 male births
- Progressive muscle weakness & life expectancy of 25-30 years
- Mutation causes skeletal muscle fibres to not be linked properly to the extracellular matrix
- Excess Ca2+ enters cells and muscle fibres die & are replaced by fat or connective tissue
- No treatment
63
What are Myostatin deficiencies?
- Myostatin normally regulates muscle growth
- Mutations in this protein results in extra muscle mass and very little body fat
- E.g. Bully whippet dog —> 3x the size of a normal dog = when homozygous are too bulky to be racers but may be good racers if heterozygous
- Also a case in humans —> Liam Hoekstra = the ‘super toddler’, strong as a 6 year old at the age of 3
64
What is the plateau phase in cardiac muscle action potentials?
Phase 2
Ca2+ channels inactivate much slower than Na+ channels so continued influx of Ca2+ occurs
65
Describe cardiac excitation contraction coupling
- Ca2+ current enters through a L-type calcium channel on the membrane of cardiac muscle (this is not linked to the ryanodine receptor directly)
- Calcium induced calcium release occurs
- This is where Ca2+ is released from the Sarcoplasmic reticulum through the Ryanodine receptor
- Receptor is triggered by the calcium current
66
How is the slope of the pacemaker potential changed?
- Via sympathetic activation —> results in steepening of the slope = increases heart rate
- Via parasympathetic activation (vagus) —> decreases the slope meaning it takes longer for the cell to get to threshold = reduces heart rate
67
How is contraction controlled in cardiac muscle?
Force of contraction is determined by:
- degree of stretch of cardiac muscle (proportional to the force the muscle will produce)
- concentration of cytoplasmic Ca2+ = can be modulated by the autonomic nervous system (sympathetic increases and parasympathetic decreases)
68
Where is smooth muscle found?
Around hollow organs
- Blood vessels
- Gut
- Bladder
- Uterus
- Bronchi
69
What is the contraction mechanism in smooth muscle?
Actin-myosin cross ridges
BUT
- contracts slowly
- more energy efficient than skeletal and cardiac
- different mechanisms for excitation-contraction coupling
- contracts well over a greater range due to different physical arrangements of actin and myosin in the smooth muscle (much less ordered)
70
What are the different sources of calcium in smooth muscle?
1. L-type calcium channels —> activated by depolarisation and triggers calcium induced calcium release via the ryanodine receptor in the Sarcoplasmic reticulum
2. IP3 receptors —> phospholipase C is activated by a GPCR (e.g. M1, M3 and M5 types of muscarinic ACh receptors) to produce IP3 which then binds to the IP3 receptor which allows Ca2+ to leave the SR
3. Store operated calcium channels —> activates when SR becomes depleted of Ca2+ and opens to allow Ca2+ into the cytoplasm
71
Role of calcium in smooth muscle
Myosin heads have much lower ATPase activity in smooth muscle, this is increased by calcium
- calmodulin interacts with the enzyme myosin light chain kinase (MLCK)
- 4x calcium bind to calmodulin
- this activates MLCK
- MLCK phosphorylates the regulatory light chains w
- which switches on the ATPase activity of the myosin heavy chain heads
- can now form cross bridges
To turn the signal off, Ca2+ must be removed and the regulatory light chains must have the phosphate group removed - this is done by myosin light-chain phosphatase
72
Describe smooth muscle excitation
- Can be myogenic —> some smooth muscles (e.g. the gut) have pacemaker-like activity
- Can be initiated by APs triggered by neuronal stimulation
- Can get APs superimposed on myogenic activity
- Can be a graded response to depolarisation (no AP)
- Can be modulated by neurotransmitters/hormones
