Muscle Physiology-Skeletal Muscle

Question 1

Skeletal muscle: Classification

Answer 1

• Striated muscle
• voluntary muscle

Question 2

Give a description of skeletal muscle

Answer 2

Bundles of long, thick, cylindrical, striated, contractile, multinucleate cells that extend the length of the muscle

Mechanical efficiency of skeletal muscle~20%

• Outer thick connective tissue layer called the epimysium
• Bundles of muscle fibres (fascicles which can twitch)
• Perimysium surrounds the bundles
• Endomysium surrounds individual muscle fibres

Question 3

Where is the typical location of skeletal muscle?

Answer 3

Attached to bones of the skeleton

Question 4

What is the function of skeletal muscle?

Answer 4

Movement of body in relation to external environment

Stabilization of joints e.g. the ankle joints (tendons run around the ankle and stabilize the joints)

Question 5

Cardiac muscle: classification

Answer 5

Striated muscle, involuntary muscle

Question 6

Give a description of cardiac muscle

Answer 6

Interlinked network of short, slender, cylindrical, striated, branched, contractile cells connected cell to cell by intercalated discs

Question 7

What is the main location of cardic muscle?

Answer 7

Wall of the heart

Question 8

What is the function of cardiac muscle?

Answer 8

Pumping of blood out of heart

Question 9

Smooth muscle: classification

Answer 9

Unstriated muscle, involuntary muscle

Question 10

Give a description of smooth muscle

Answer 10

Loose network of short, slender, spindle- shaped, unstriated, contractile cells that are arranged in sheets

Question 11

Where is a typical location of smooth muscle?

Answer 11

Walls of hollow organs and tubes, such as stomach and blood vessels

Question 12

What is the function of smooth muscle?

Answer 12

Movement of contents within hollow organs and blood vessels

Question 13

Lists some functions of skeletal muscle

What is the mechanical efficiency of skeletal muscle?

Answer 13

• Movement
• Stability of Joints
• Posture
• Heat generation

Mechanical efficiency of skeletal muscle = ~ 20%

Question 14

What is a fasciculation?

Answer 14

A fasciculation, or muscle twitch, is a small, local, involuntary muscle contraction and relaxation which may be visible under the skin e.g. motor neurone disease (MND)

Question 15

Explain the structure of myofibrils

Answer 15

• Striated pattern of myofibrils
• Dark band called the A band, light band called the I band
• Sarcomere is one unit from one Z disk to another

Question 16

Describe the gross anatomy of skeletal muscle

Answer 16

Question 17

What is the structure of skeletal muscle fibres (banding)?

Answer 17

The Z line appears as a series of dark lines; they act as an anchoring point of the actin filaments

H-band is the zone of the thick filaments that has no actin. Within the H-zone is a thin M-line formed of cross-connecting elements of the cytoskeleton

Question 18

Show a TEM of skeletal muscle sarcomere with diagrammatic representation of component myofilaments.

Answer 18

Question 19

Explain the Sliding filament theory of muscle contraction

Who came up with this theory?

Answer 19

During muscle contraction the thin actin filaments slide over the thick myosin filament:

1. Ca²⁺ ions are released from the sarcoplasmic reticulum into the sarcoplasm
2. The breakdown of ATP releases energy, releasing the myosin head
3. Ca²⁺ ions bind to troponin, exposing the binding site on the actin filament
4. The myosin head attaches to the exposed binding site on the actin filament forming a crossbridge
5. Flexing of the cross bridge pulls the actin filament towards the center of the sarcomere (m line)
6. An ATP molecule reattaches to the binding site on the myosin head
7. The myosin head is released from actin filaments binding site which is covered up again

Theory by Huxley

Question 20

What observation supports the sliding filament theory?

Answer 20

I band gets shorter but the A band stays the same width

Question 21

What happens when skeletal muscle filaments contract?

Answer 21

During contraction

• I band shortens
• Sarcomere shortens
• A band stays the same width

Question 22

Bands and Cross-Bridges: A and I bands

Answer 22

• A band: thick filaments along with portions of thin filaments that overlap
• I band: remaining portion of thin filaments that do not project into A band

Question 23

Bands and Cross-Bridges: Cross-bridges

Answer 23

• Project from each thick filament in six directions toward the surrounding thin filaments
• The attachment of a myosin head from the thick filament to an active site on actin on the thin filament is a cross bridge. As soon as the cross bridge forms, the power stroke occurs, moving the thin filament toward the center of the sarcomere

Question 24

Myosin and Actin:

Which filaments does myosin form?

Which filaments does actin form?

What other proteins are associated with actin?

Answer 24

• Myosin forms thick filaments:

Protein consisting of two identical subunits, each shaped somewhat like a golf club

• Actin (forms helices) is the main structural component of thin filaments:

Interacts with the myosin cross-bridges

Two other proteins, tropomyosin and troponin, are associated with actin

Question 25

Describe the Molecular Basis of Skeletal Muscle Contraction: What happens during contraction? What is the sliding filament mechanism? What is the power stroke?

Answer 25

During contraction, cycles of cross-bridge binding and bending pull thin filaments inward * Sliding filament mechanism: Contraction is accomplished by thin filaments from the opposite sides of each sarcomere sliding closer together between the thick filaments * Power stroke: Binding of myosin heads pulls the thin filament toward the center of the sarcomere Occurs at the release of phosphate and ADP from the myosin molecule after the ATP hydrolysis while myosin is tightly bound to actin

Question 26

Sliding Filament Theory: Thin filament What does TnI, TnT, and TnC bind to?

Answer 26

Actin, tropomyosin and troponin (TnI-actin, TnT-tropmyosin TnC-calcium ions) molecules complex to form the thin filaments of skeletal muscle

Question 27

Sliding Filament Theory: Thick filaments Describe the structure of myosin

Answer 27

* An individual myosin molecule has a rod-like structure from which two 'heads’ protrude. * Each thick filament consists of many myosin molecules, whose heads protrude at opposite ends of the filament.. Myosin: Long tail (pairs of heads that can interact with 6 thin filaments that run past them)

Question 28

Draw a myosin molecule and a thick filament: What sites does myosin contain?

Answer 28

* Actin binding site on the myosin head * ATPase site on the myosin head * 2 hinges that allow myosin to bend at 2 places

Question 29

The actin filament forms a helix: How are troponin and tropomyosin involved?

Answer 29

* Tropomyosin molecules coil around the actin helix, reinforcing it. * A troponin complex is attached to each tropomyosin molecule.

Question 30

Cross bridge activity: all cross-bridge stroking directed toward center of thick filament

Answer 30

(a) During each cross-bridge cycle, the cross bridge binds with an actin molecule, bends to pull the thin filament inward during the power stroke, then detaches and returns to its resting conformation, ready to repeat the cycle. (b) The power strokes of all cross bridges extending from a thick filament are directed toward the center of the thick filament (towards the m line). (c) All six thin filaments surrounding each end of a thick filament are pulled inward simultaneously through crossbridge cycling during muscle contraction

Question 31

Describe the role of Calcium Ions in the Contraction Mechanism

Answer 31

* Views a-d are cross-sectional views of the thin actin filament. * At rest the tropomyosin as blocking the actin binding sites so it cant bind to actin. * When increased intracelleular concentration of calcium ions bind to TnC of troponin, a conformational change moves tropomyosin away from myosin’s binding sites. * This displacement allows myosin heads to bind actin, and contraction begins. * To return to relaxation, the calcium concentration simply needs to be decreased

Question 32

What are the sequence of events involved in the sliding of the thin filaments during contraction?

Answer 32

This occurs only in the presence of Ca2+, which releases tropomyosin’s blockade of actin’s active sites 1. Myosin cross bridge attaches to the myofilament 2. Working stroke- the myosin head pivots and bends as it pulls on the actin filament sliding it toward the M line 3. As new ATP attaches to the myosin head, the cross bridge detaches 4. As ATP is split into ADP and Pi cocking of the myosin head occurs

Question 33

Give a detailed explanation of the steps in contraction

Answer 33

**Energized:** ATP split by myosin's ATPase; ADP and Pi remain attached to myosin; energy stored in cross bridge (that is, energy “cocks” cross bridge). **Binding:** Ca2+ released on excitation; removes inhibitory influence from actin, enabling it to bind with cross bridge. **Resting:** No excitation; no Ca2+ released; actin and myosin prevented from binding; no cross-bridge cycle; muscle fiber remains at rest **Bending:** Power stroke of cross bridge triggered on contact between myosin and actin; Pi released during and ADP released after power stroke. **Rigor complex:** If no fresh ATP available (after death), actin and myosin remain bound in rigor complex (rigor mortis- 'the stiffness of death') **Detachment:** Linkage between actin and myosin broken as fresh molecule of ATP binds to myosin cross bridge; cross bridge assumes original conformation; ATP hydrolyzed

Question 34

What neurotransmiters and receptors are involved at a neuromuscular junction?

Answer 34

* Ach - acetylcholine (neurotransmitter) * Cholinergic synapse * Nicotinic receptors – ligand-gated Na+ channels * Ache - acetylcholinesterase (enzyme)

Question 35

Describe Excitation-Contraction Coupling

Answer 35

* At each junction of an A band and I band, the surface membrane dips into the muscle fiber to form a transverse tubule (T tubule), which runs perpendicularly from the surface of the muscle cell membrane into the central portions of the muscle fiber * Because the T tubule membrane is continuous with the sarcolemma, an action potential on the surface membrane spreads down into the T tubule, rapidly transmitting the surface electrical activity into the interior of the fiber. * The presence of a local action potential in the T tubules leads to permeability changes in a separate membranous network within the muscle fiber, the sarcoplasmic reticulum

Question 36

What does the surface membrane of muscle fiber look like?

Answer 36

From the diagram: * Sarcoplasmic retiuculm shown in green * The transverse (T) tubules are membranous, perpendicular extensions of the surface membrane that dip deep into the muscle fiber at the junctions between the A and I bands of the myofibrils. * The sarcoplasmic reticulum (SR) is a fine, membranous network that runs longitudinally and surrounds each myofibril, with separate segments encircling each A band and I band. * The ends of each segment are expanded to form lateral sacs that lie next to the adjacent T tubules

Question 37

What are the steps that lead to ca²⁺ release channels in sarcoplasmic reticulum

Answer 37

1. There are voltage-gated dihydropyridine receptors in the T tubule 2. Foot proteins (ryanodine receptors) serve as Ca²⁺ release channles in sarcoplasmic reticulum 3. Activation of L-type dihydropyridine receptors (volatge gated) on by local action poteintial in T tubule triggers opening of ryanodine receptor channels in the sarcoplasmic reticulum 4. (Dihydropyrdine receptors physically coupled to the ryanodine receptors so they can mechanically open them) 5. Ca²⁺ enters the cytosol from the sarcoplasmic reticulum

Question 38

Calcium is the Link between Excitation and Contraction

Answer 38

* Spread of action potential down transverse tubules * Calcium release from sarcoplasmic reticulum * ATP-powered cross-bridge cycling * Relaxation caused by decreased [Ca²⁺] * Contractile activity far outlasts the electrical activity that initiated it

Question 39

Draw graphs for contracile response

Answer 39

\* 1 AP down the muscle= 1 twitch

Question 40

Explain the relaxation of Muscle: What happens to CA²⁺ ions?

Answer 40

* Ca²⁺ is pumped back into the SR via Ca²⁺ pumps: * Sarco (Endo) Plasmic Reticulum Calcium ATPases * (SERCA pumps) * Some Ca²⁺ can bind to calmodulin

Question 41

Explain contracture (rather than contraction)

Answer 41

* a state of continuous contraction * occurs when ATP is depleted, as myosin cross bridges are unable to detach from actin filaments **rigor mortis** (the stiffness of death) can determine time of death by looking at rigor mortis (for about 24 hours after death)

Question 42

What is fasciculation?

Answer 42

Associated with motor neurone disease and causes your muscles twitch excessively

Question 43

Explain the sliding filament mechanism

Answer 43

* The thin filaments on each side of a sarcomere slide inward over the stationary thick filaments toward the A band’s center during contraction * As they slide inward, the thin filaments pull the Z lines to which they are attached closer together, so the sarcomere shortens. As all sarcomeres throughout the muscle fiber’s length shorten simultaneously, the entire fiber shortens. * This is the sliding filament mechanism of muscle contraction. The H zone, in the center of the A band where the thin filaments do not reach, becomes smaller as the thin filaments approach each other when they slide more deeply inward. * The I band, which consists of the portions of the thin filaments that do not overlap with the thick filaments, narrows as the thin filaments further overlap the thick filaments during their inward slide. * The thin filaments themselves do not change length during muscle fiber shortening. The width of the A band remains unchanged during contraction because its width is determined by the length of the thick filaments, and the thick filaments do not change length during the shortening process. * Note that neither the thick nor the thin filaments decrease in length to shorten the sarcomere. Instead, contraction is accomplished by the thin filaments from the opposite sides of each sarcomere sliding closer together between the thick filaments

Question 44

If Ca²⁺ is present is the actin binding site blocked or cleared?

Answer 44

When Calcium is present the blocked active site clears

Question 45

Explain actin-myosin interaction in contraction

Answer 45

* **Attached:** at the start of cycle showing this figure, a myosin head lacking a bound nucleotide is locked tightly onto an actin filament in a rigor configuration. In an actively contracting muscle this state is very short lived, being rapidly terminated by the binding of a molecule of ATP. * **Released:** a molecule of ATP binds to the large cleft on the back of the head and immediately causes a slight change in the conformation of the domains that make up the actin-binding site. This reduces the affinity of the head for actin and allows it to move along the filament. * **Cocked:** the cleft closes like a clam shell around the ATP molecule, triggering a large shape change that caused the heard to be displaced along the filament by a distance of about 5nm. Hydrolysis of ATP occurs, but the ADP and Pi produced remain tightly bound to the protein. * **Force-generating:** the weak binding of the myosin head to a new site on the act filament causes release of the inorganic phosphate produced by ATP hydrolysis, concomitantly with the tight binding of the head to actin. This release triggers the **power stroke** -the force-generating change in shape during which the head regains its original conformation. In the course of the power stroke, the head loses its bound ADP, thereby returning to the start of the cycle ‘Attached’.

Question 46

Are there thick filaments in the center of the sarcomere? ## Footnote Where do the myosin heads extend toward the actin filaments?

Answer 46

In the centre of the sarcomere the thick filaments are devoid of myosin heads. The myosin heads extend towards the actin filaments in regions of potential overlap.