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MSK > 19 - Skeletal Muscle Contraction > Flashcards

19 - Skeletal Muscle Contraction Flashcards

1
Q

What do I need to know?

A
  1. Structural components
  2. Myofibre ultrastructure
  3. The contractile proteins
  4. X Bridge Cycle
  5. Contractile Process (ECC, role of Ca, time course of activation)
  6. Modulation of force (summation and tetanus, sympathetic stimulation)
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2
Q

What are 4 characteristics of skeletal muscle?

A

Excitable
Contractile
Extensible
Elastic

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3
Q

What is the morphological classification of muscles?

A

(based on structure)
Striated (cardiac and skeletal)
Non-striated (smooth)

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4
Q

Functional classification of muscles?

A

Voluntary - skel

Non-vol - cardiac and smooth

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5
Q

What components do excitable cells have?

A
  • RMP (the balance of ions across the cell membrane) of about -80mV
  • high Ca and Na extracellular
  • high K intracellular
  • ATPases and Na/Ca exchangers maintain the balance
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6
Q

What CT is each muscle wrapped in?
What is each fasicle of muscle fibres wrapped in?
What is each muscle fibre/myofibril wrapped in and what lies beneath it?

A
  • epimysium
  • perimysium
  • endomysium
  • sarcolemma/plasma membrane of the myofibril
  • blood vessels run in between the CT layers
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7
Q

Summarise the ultrastructure of skeletal muscle fibres

A
  • are innervated by alpha motor neurons
  • NOT branched
  • the fibres make up 75 - 90% of total muscle volume
  • are 75% water (sarcoplasm/cytoplasm)
  • are multinucleate with peripheral nuclei
  • long and cylindrical
  • diameter is 10-100 um (small)
  • there are no cellular connections to adjacent cells; this means they can belong to different motor units and one cell can contract and the adjacent one may not
  • striated due to arrangement of contractile protein filaments
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8
Q

What is the sarcolemma?

A

Is the cell membrane of muscle cells

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9
Q

What are transverse (T) tubules and what do they allow?

A
  • Invaginations of the surface sarcolemma that penetrate to the centre of the muscle cell
  • they are in continuation with the extracellular space
  • they allow the action potential to propagate through the entire cell so the cell and filaments contracts synchronously
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10
Q

What are longitudinal tubules?

A

They are part of the T-Tubule system that link the T Tubules (is sarcoplasm reticulum)

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11
Q

Describe the intracellular structure of a myocyte

A
  • the contractile myofilaments in the cell (actin/myosin) are organised into bundles called myofibrils
  • there are many myofilaments in a myofibril and many myofibrils in a myocyte
  • the myofilaments form different zones of different dimensions depending on if the muscle is contracted or relaxed
  • the myofilaments interdigitate in a strict geometry
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12
Q

What is the sarcoplasm reticulum?

A
  • It is an intracellular membrane bound system that stores calcium.
  • It lies on either side of a T Tubule and webs around the myofibrils
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13
Q

What does a triad consist of?

A
  • a t tubule
  • terminal cisterna on either side
    > the terminal cisterna interacts with the T Tubule membrane channels to initiate the calcium release into the muscle cell
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14
Q

What is the triad essential for?

A

The triad is essential for synchronised excitation-contraction coupling (ECC)

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15
Q

How does the SR provide feedback control in order to balance in the intracellular calcium levels?

A

Through the use of 3 SR calcium-regulatory proteins

  1. Luminal Calcium Binding Proteins for calcium storage (calsequestrin eg.)
  2. SR Calcium release channels (Ryanodine Receptors - RyR1 and IP3 receptors) for calcium release
  3. SR Calcium ATPase pumps (SERCA) for Ca re-uptake into the SR
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16
Q

What is a sarcomere?

A

Contractile unit of a myofibre. Make up a myofibril and are made of myofilaments

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17
Q

What is the organisation of a sarcomere?

A

A Band: both think and thin filaments overlapping
I Band: Only thin (have opposite polarity on either side of the Z line)
Z Disc: an electron dense region at the middle of the I band where actin/thin filaments of opposing polarity attach. Distance between Z Discs is a sarcomere
H Band: Centre of the A Band with only thick filaments
M Line: electron dense region where myosin/thick filaments of opposing polarity attach

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18
Q

What do the thick filaments consist of?

A
  • 100s of myosin molecules
  • at the M line are orientated in opposite directions
  • is repeated, staggering PAIRED myosin heads with each pair 14.3nm apart and displaced 60 degrees to the next
  • diameter: 15nm
  • length: 1600nm
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19
Q

Where is there a bare zone of myosin heads?

A

H zone (mostly)/in the middle either side of the M Line

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20
Q

What does the hinge region of myosin filaments allow?

A

Enables movement once the filament is attached to actin

21
Q

What is Titin and what is its purpose?

A
  • Titin acts as a spring/tether connecting the end of the thick filament to the Z disc
  • contributes to passive force
  • maintains structural integrity of the sarcomere during contraction
22
Q

What do the thin filaments consist of?

A
  • 2 strands of actin filaments twisted into a helix
  • nebulin protein lies between the 2 actin filaments in the helix to align the filaments
  • the filaments are each composed of Globular actin molecules
  • diameter: 7nm
  • length: 1000nm
23
Q

What does nebulin do?

A

Is a structural protein that lies between the 2 actin filaments and helps align them

24
Q

What is tropomyosin?

A
  • a rod shaped molecule that lies on top of each of the 2 F-actin in a groove
  • each tropomyosin is associated with 3 other proteins; the troponin complex
25
Q

What makes up the troponin complex?

A

TnT (troponin-tropomyosin):
> positions the troponin complex on the tropomyosin
TnC (troponin-calcium):
> contains the calcium binding sites
TnI (troponin-inhibitor):
> BINDS to actin and inhibits myosin heads from binding to actin and forming a cross bridge

26
Q

What makes up the calcium sensitive switch?

A

The troponin complex and tropomyosin (thin filament)

27
Q

Why are there so many regulatory proteins?

A

Muscle is constantly moving so need to maintain the structural integrity during contraction. More to do with thin filaments

28
Q

What initiates cross bridge cycling?

A

An increase in cytosolic calcium initiates cross bridge cycling and BINDING of an ENERGISED myosin cross bridge to actin

29
Q

When is myosin energised and have high affinity for actin?

A

When ATP has been hydrolysed and so has bound ADP + P

30
Q

What are the 6 steps of the X Bridge Cycle?

A
  1. NO ATP and NO Ca bound means the the myosin head is tightly bound to actin in the RIGOR state. Cross-bridge is at 45 degrees relative to the thick filament
  2. ATP binds to the nucleotide binding site on myosin, reduces its affinity for actin and so dissociates from actin
  3. ATPase activity of the myosin head hydrolyses ATP > ADP + P bound to myosin head. No Ca still. The myosin ADP + P complex has a high affinity for actin so…
  4. Myosin head swings and binds weakly to the next actin molecule to form a cross bridge at 90 degrees
    > calcium increase and tropomyosin moves off actin
  5. ADP and P is released, initiating the POWER STROKE where the myosin head rotates on its hinge and pulls the actin filament to it (45 degrees)
  6. ADP is released and the myosin head is in the tightly bound rigor state
31
Q

What does the ability of a muscle fibre to develop force depend on?

A

The interaction between the contractile myofilaments actin and myosin

32
Q

What does the power stroke achieve and when does it occur?

A

When P is released, causes the myosin head to rotate on its hinge. As the 2 ends are orientated in opposite directions this brings the Z discs together and is the force generating step.

33
Q

What are the 2 roles of calcium in the cross bridge cycle?

A
  1. ATP binding to the myosin head breaks the X bridge by decreasing the affinity for actin, allowing the cycle to repeat
  2. ATP hydrolysis provides the energy for power stroke and cross bridge movement
34
Q

What is the contractile process mostly dependent on?

A

Calcium influx as ATP is normally high in the cell

35
Q

What is the role of calcium in the contractile process?

A

> normally low in the cell so the troponin complex and tropomyosin inhibit cross bridge formation
when calcium influxes, the troponin-tropomyosin complex moves and exposes the myosin binding sites on G-actin allowing X Bridge

36
Q

What happens when the calcium levels increase?

A

> calcium binds to Troponin C on 4 sites co-operatively creating a sigmoidal curve
TnC has 2 high affinity binding sites always occupied by Ca/Mg and 2 low affinity sites that initiate the shift of tropomyosin via a conformational change
when the 4 sites on TnC are filled the inhibition of TnI is released

37
Q

How is intracellular calcium kept low?

A

By SERCA pumps in the SR

38
Q

What brings about the increase in calcium to initiate X Bridge?

A

> opposite 4 RyR monomers of the SR is a high concentration/tetrad of dihydropyridine receptors (DHPRs) in the T Tubules
together the RyRs and DHPRs function as a single calcium release channel
depolarisation causes a conformational change in the L Type DHPRs/Calcium channels in the T Tubules
the calcium release of this channel is slow so there is no great influx and it is not functional
instead the DHPR interacts with the cytoplasmic foot of the RyR of the SR causing it to open and calcium influxes

39
Q

What are Ryanodine Receptors? (RyRs)

A

> In an electron microscope you can see electron dense feet that extend from the junctional terminal cisternae of the SR to the T Tubules at the triad
they are the CALCIUM RELEASE channels of the SR

40
Q

What are dihydropyridine receptors (DHPRs)?

A

> in the T Tubules
L Type voltage dependent calcium channels
have very slow activation kinetics
consists of 4 homologous repeats and 4 are clustered together to form a tetrad
opposite these are 4 RyR monomers

41
Q

What are calsequestrin proteins?

A

Proteins in the SR which bind calcium

42
Q

What inhibits RyR channels of the SR?

A

Mg - voltage sensor activation overcomes this inhibition via interaction with the DHPR

43
Q

What is the duration of an action potential in nerve and muscle cell compared to muscle contraction?

A
  • duration of the AP is short 2ms

- contraction in the muscle is much longer in response 10-100ms

44
Q

What is the consequence of contraction being much longer than an AP?

A

> it means that the membrane is fully repolarized BEFORE the peak of contraction in the muscle
this enables force development in muscle through summation and tetany to be varied

45
Q

How do you get a summation of force in muscle?

A

Stimulate the muscle with an action potential before the muscle has relaxed

46
Q

What is an unfused tetanus?

A

Is where the stimuli is far enough apart that the muscle relaxes slightly. Results in the maximum tension achieved being much more than in single twitches

47
Q

What is summation leading to fused tetanus?

A

> Stimuli is closer together, there are many calcium release events and doesn’t relax. Instead muscle reaches steady tension and achieves maximum force
fatigue will cause the muscle to lose tension despite continuing stimuli

48
Q

How does skeletal muscle usually work?

A

Fused tetanus

49
Q

What are the 2 ways to vary muscle force?

A
  1. Motor unit recruitment

2. Via summation and increasing the frequency of action potentials/stimuli

MSK (29 decks)

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