Skeletal muscle 2: Skeletal muscle contraction

Question 1

Do skeletal muscle fibres branch?

Answer 1

No

Question 2

Describe the connective tissue of the muscle fibres;

Answer 2

Epimysium (surrounds muscles)
Perimysium (surrounds muscle bundles or fascicles)
Endomysium (surrounds each muscle fibres)

Question 3

Can muscles regenerate?

Answer 3

Muscle tissue contains satellite cells which can help regenerate the tissue.

Question 4

What is the name of the cell membrane of muscle cells;

Answer 4

Cell membrane
Plasmamembrane
SARCOLEMMA

Question 5

What are distinct features of the plasma membrane?

Answer 5

T-tubules. Deep invaginations that propagate action potentials. In continuity with extracellular space. Perpendicular to sarcolemma.

Question 6

What is a muscle fibre?

Answer 6

One cell with many fibrils. Hence T tubule system.

Question 7

Describe the ultrastructural appearance of skeletal muscle;

Answer 7

• Striated appearance because of highly ordered sarcomeric proteins.
• 100um in diam and up to severeal cm in length.
• Multinucleated, found peripherally.

Question 8

What is the SR?

Answer 8

Intracellular store of Ca

Question 9

What are the terminal enlargements of the SR known as?

Answer 9

Terminal cisternae. Essential for synchronised EC coupling.

Question 10

What are the 3 major SR-Ca regulatory proteins?

Answer 10

1) Luminal Ca binding proteins i.e Calsequestrin
2) SR Ca release channels i.e RYR1 or IP3 receptors
3) SERCA pumps

Question 11

Describe the features of sarcomere;

Answer 11

A-Band; Thick and thin filament overlap
I-band; Only thin filaments
Z-Line; Actin filaments attach
H-band; Thick filaments only
M-line; Myosin filaments attach.

Question 12

What are the thick filaments?

Answer 12

Myosin

Titan acts as an adjustable molecular spring during contraction.

Question 13

What does titan contribute to?

Answer 13

Passive force and maintaining structural integrity of the filaments.

Question 14

What comprises thin filaments?

Answer 14

• Two strands of F-actin twisted together into a helix
• Tropomyosin (Tm) lies along the F-actin groove.
• Nebulin aligns the actin filaments.

Fibrous and Globular Actin

Question 15

What is the function of tropomyosin?

Answer 15

Each tropomyosin molecule is associated with 3 other proteins which forms the troponin complex. TnT, TnC and TnL.

Question 16

Describe the crossbridge cycle;

Answer 16

• ATP binds myosin and is hydrolysed, forming a high free energy state. The myosin has high affinity for actin.
• Myosin binds readily in the preferred 90 degree orientation.
• With the released of the bound ADP-Pi, the free energy of the myosin-actin complex has a minimum at a 45degree angle.
• The rotation from the original 90 degree orientation to the low energy 45 degree orientation (while the myosin head is attached to actin) leads to the force developed and shortening.
• ATP binding reduces affinity of myosin for actin and crossbridge detaches. In the absence of ATP the cross bridge cannot detach and this leads to rigor.

Question 17

What is the role of Ca in the contraction process?

Answer 17

• At rest tropomyosin prevents interaction between actin and myosin.
• When cytosolic Ca increases, four Ca ions bind troponin C, causing the troponin complex to change conformational state. The tropomyosin molecule then shifts with respect to the actin filament, removing the steric interface to cross bridge interaction.

Question 18

What are the requirements for crossbridge cycling?

Answer 18

• Cross bridge cycling generates force as a long as Ca remains high and ATP is present.

Question 19

What maintains cytosolic Ca levels?

Answer 19

SERCA maintains Ca at very low levels. High affinity for Ca.

Ca binds calsequestrin at its release sites in the terminal cisternae.

Question 20

What is the mechanical coupling hypothesis?

Answer 20

• The high density of DHPR (Ca voltage gated) receptrers in the T-tubules opposite the RyRs in the SR terminal cisternae.
• DHPR essential for EC coupling.
• Depolarisation of the TT membrane flips the DHPR which induces a conformational change of the RyR in the terminal cisternae to a high conductance open state.

Voltage dependent calcium release.

Question 21

Whats the benefit of voltage dependant EC coupling?

Answer 21

• Rapid kinetics
• No dependence on current flow
• No reliance on diffusion
• Activation can therefore occur in the absence of extracellular Ca.

Question 22

Whats the time course of EC coupling?

Answer 22

AP (2ms)
Latent phase
Contraction-Relaxation phase 10-100ms.

Question 23

What is summation?

Answer 23

Stimuli close together, does not allow full relaxation

Question 24

What is unfused tetanus?

Answer 24

Stimuli far enough apart to allow the muscle to relax slightly whilst at maximal tension.

Question 25

What is fused tetanus?

Answer 25

Stimuli frequent enough reaching steady tetanus until fatigue sets in.

Question 26

How can the sympathetic nervous system impact the Sm contraction?

Answer 26

Directly affects the muscle fibres. Effects vary depending on fast or slow fibres.

Catecholamines;

Fast twitch; Peaked tension in response to single stimulus is increased, time course decreased.

Slow twitch; catecholamines reduce peak tension and prolong time course. Hence following stress postural muscles can feel weak.