Contraction of Skeletal Muscle

Question 1

Myofibrils, Actin and Myosin Filaments

Answer 1

Each myofibril is composed of about 1500 adjacent myosin filaments and 3000 actin filaments

Filaments partially interdigitate:

• light bands contain only actin filaments and are called I bands
• dark bands contain myosin filaments, as well as the ends of the actin filaments where they overlap the myosin, and are called A bands

Interaction between cross-bridges and the actin filaments that cause contraction

Z discs attach the myofibrils to one another all the way across the muscle fiber

Bands give skeletal and cardiac muscle their striated appearance

Portion that lies between two successive Z discs is called a sacromere

Question 2

Titin

Answer 2

Springy titin molecules act as a framework that holds the myosin and actin filaments in place

Question 3

Sacroplasm

Answer 3

Spaces between myofibrils are filled with intracellular fluid containing large quantities of K, Mg, and Phosphate, plus multiple protein enzymes

Also present are mitochondria that lie parallel to the myofibrils and supply the contracting myofibrils with ATP

Question 4

Sacroplasmic Reticulum

Answer 4

In the sacroplasm surrounding the myofibrils. This reticulum has a special organization important in controling muscle contraction

Question 5

General Mechanism of Muscle Contraction

Answer 5

1. An AP travels along a motor nerve to muscle fibers
2. At each ending, the nerve secretes a small amount of the nuerotransmittre substance acetylcholine
3. The ACh acts on a local area of the muscle fiber membrane to open multiple ACh gated channels through protein molecules floating in the membrane
4. Large quantities of Na ion diffuse to the interior of the muscle fiber membrane inititating an AP at the membrane
5. AP travels along the muscle fiber membrane
6. AP depolarizes the muscle membrane, with much of AP electricity flowing through the center of the muscle fiber
   
   1. causing sacroplasmic reticulum to realease large quantities of Ca2+ ions
7. Ca2+ initiate attractive forces b/w the actin and myosin filaments, causing them to slide alongside each other - contraction
8. After a fraction of a second, Ca pumped back into the sacroplasmic reticulum by a Ca++ membrane pump where they are stored into a new muscle AP comes along
   
   1. causes the muscle contraction to cease

Question 6

Sliding Filament Mechanism

Answer 6

Forces generated by interaction ofthe cross-bridges from the myosin filaments with the actin filaments.

Calcium ions activate the forces between the myosin and actin filaments, and contraction begins.

Question 7

Myosin Filament

Answer 7

• Myosin molecule composed of two heavy chains and four light chains
• Two heavy chains wrap spirally around each other to form a double helix - tail of myosin molecule
• One end of each of these chains is folded bilaterally into a globular myosin head
• Four light chains are part of the myosin head, two to each head.
  
  • help control function of the head during constraction
• The protruding arms and heads together are called cross-bridges - flexible at two points called hinges
• No cross-bridges heads in the very center of the myosin filament because the hinged arms extend away from the center

Question 8

Actin Filament

Answer 8

• Composed of 3 proteins: actin, tropomyosin and troponin
• Backbone of actin filament is a double stranded F-actin molecule
  
  • each F-actin helix is composed of polymerized G-actin molecules (ADP attached)
• ADP molecules are the active sites on the actin filaments with which the cross-bridges of the myosin filament interact to cause muscle contraction

Question 9

Tropomyosin Molecules

Answer 9

• wrapped spirally around the sides of the F-actin helix
• In resting state - lie on top of the active sites of the actin strands, so that attraction can’t occur b/w actin and myosin

Question 10

Troponin

Answer 10

• Attacahed intermittently along the sides of the tropomyosin molecuels
• complexes of 3 loosely bound protein subunits, each of which plays a specific role in controlling muscle contraction
• Complex is believed to attach the tropomyosin to the actin
  
  • strong affinity of the troponin for calcium ions is believed to initiate the contraction process

Question 11

Activation by Ca+ ions on troponin-tropomyson

Answer 11

In the presence of Ca++ ions, the inhibitory effect of the troponin-tropomyosin on the actin filaments is itself inhibited

• When Ca combines w/ troponin C, the troponin complex undergoes a conformational change that in some way tugs on the tropomyosin molecules and moves it deeper into the groove between the two actin strands
• This uncovers the active sites of the actin, thus allowing these to attract the myosin cross-bridge heads and cause contraction to proceed

Question 12

Activated Actin Filament and Myosin Cross-Bridges

Answer 12

Heads of cross bridges become attracted to the active sites of the actin filament

Walk-Along Theory

• Postulated that when a head attaches to an active site, this attachment simultaneoulsy causes profound changes in the intramolecular forces between the head and arm of its cross bridge
• New alignment of forces causes the head to tilt toward the arm and to drag the actin filament along with it
• Tilt of the head = power stroke
• Immediately after tilting, the automatically breaks away from the active site and combines with a new active site farther down along the actin filament
• Pulling the ends of two successive actin filaments toward the center of the myosin filament
• The greater the number of cross-bridges at any given time, the greater force of contraction

Question 13

Chemical events in the motion of myosin heads

Answer 13

1. Before contraction begins, the heads of cross-bridges bind with ATP. ATPase activity of the myosin head immeadietely cleaves the ATP but leaves the cleavage products, ADP plus phosphate ion, bound to the head (not yet attached to actin)
2. myosin heads bind with active sites when troponin-tropomyosin binds Ca++
3. Bond causes conformational change in the head, prompting the head to tilt toward the arm - (Power stroke) The energy that activates the power stroke is the energy already stored
4. Once the head titls, this allows release of the ADP and phosphate ion, a new molecule of ATP binds causing detachment of the head from the actin
5. ATP is cleaved to begin the next cycle
6. When the cocked head (with stored energy derived from the cleaved ATP) binds with a new active site, it becomes uncocked and once again provides a new power stroke

Question 14

Relation of Velocity of Contraction to Load

Answer 14

• A skeletal muscle contracts extremely rapidly when it contracts against no load
• When loads are applied, the velocity of contraction becomes progressively less as the load increases
• When the load has increased to equal the maximum froce that the muscle can exert, the velocity of contraction becomes zero and no contraction resuts, despite activation of the muscle fiber

Question 15

Role of ATP

Answer 15

• Pumps calcium ions from the sacroplasm into the sacroplasmic reticulum after the contraction is over
• pumping sodium and potassium ions through the muscle fiber membrane to maintain appropriate ionic environment for propagation of muscle fiber APs

Question 16

Isometric vs. Isotonic Contraction

Answer 16

Isometric

• When the muscle does not shorten during contraction

Isotonic

• When it does shorten but the tension on the muscle remains constant through the contraction

Question 17

Mechanics of Skeletal Muscle Contraction - Summation

Answer 17

Summation means the adding together of individual twitch contractions to increase the intensity of overall muscle contraction

Occurs by

• increasing the number of motor units contracting simultaneousley (multiple fiber summation)
• increasing the frequency of contraction, (frequency summation - can lead to tetanization)

*All the muscle fibers innervated by a single nerve fiber are called a motor unit

Question 18

Frequency Summation and Tetanization

Answer 18

As the frequency increaes, there comes a point where each new contraction occurs before the preceding one is over

• as a result, the second contraction is added partially to the first so that the total strength of contraction rises progressively with increasing frequency
• When freq reaches a critical level, the successive contractions eventaully become so rapid that they fuse together and the whole muscle contraction appears to be completely smooth and continuous - **tetanization **
  
  • any increase in frequency beyond that point has no further effect in increasing contractile force
  • occurs through supply of Ca++ ions in sacroplasm

Question 19

Fast vs Slow Fibers

Answer 19

Muscles that react rapidly are composed of mainly fast fibers with only small numbers of the slow variety

The mucscles that respond slowly but with prolonged contraction are composed mainly of slow fibers

Fast Fibers

• Large fibers for great strength
• extensive SR for rapid release of calcium ions
• large amount of glycolytic enzymes for rapid release of energy
• less extensive blood supply because oxidative metabolism is of secondary important
• fewer mitochondria ^
• no red myoglobin hence white muscle

Slow Fibers

• Small fibers innervated by smaller nerves
• more extensive blood vessel system to supply extra amounts of O2
• increased numbers of mitochondria
• contain large amounts of myoglobin
  
  • gives slow muscle a reddish appearance