1. Skeletal Muscle Structure – Molecular Level
Titin
Connects myosin to the Z-lines in the sarcomere
It is very elastic
Able to stretch up to 3 times its resting length
Important molecule because it is responsible for muscle flexibility

3. Skeletal Muscle Contraction – Force Generation
Chemical or heat energy in the body is converted to mechanical work or movement.
A nerve impulse arrives at the neuromuscular junction (NMJ) and stimulates the beginning of the contraction process
NMJ = synapse between a motor neuron and a skeletal muscle cell
Stimulation of the skeletal muscle cell triggers the release of calcium ions from the terminal cisternae of the sarcoplasmic reticulum
Calcium catalyzes the contraction process

4. Skeletal Muscle Contraction – Force Generation
Calcium ions bind to troponin
Troponin then pushes tropomyosin away thus exposing the active site that it is covering on actin
Myosin crossbridges have a strong affinity for the exposed active site on the actin molecule
Myosin binds to the exposed active site
Myosin crossbridges pull on the actin myofilament pulling it toward the center of the sarcomere
This motion physically shortens the sarcomere, the myofibril, and the muscle fiber.

6. “Sliding Filament” Mechanism
Contraction results from the sliding action of interdigitating actin and myosin filaments
RELAXED:
CONTRACTED:

8. The Sliding-Filament Model
A muscle contracts because the myosin and actin myofilaments slide past each other
Myosin cross bridges attach and pull, release, reattach and pull, sliding the actin toward the center of the sarcomere
Results in shortening of the I-band and the H-zone
Neither actin nor myosin actually change length even though the sarcomere is shortened in the contraction process
The A-band remains the same length (length of myosin)
A single attachment of the cross bridge results in about a 1% shortening of the total muscle
Muscles normally shorten 35 to 50% of their total resting length

9. The Sliding-Filament Model
Each myosin cross bridge must attach and reattach many times during a single contraction
Called crossbridge cycling
Power Stroke - Attachment of the myosin cross bridge to actin requires energy
Breakdown of ATP into ADP and P provides the energy required for pulling on the actin myofilament
ATP-ase catalyzes the breakdown of ATP
Rigor – low-energy, strong bond between myosin and actin
ADP and P are released from the myosin head thus breaking the bond between the myosin crossbridge and actin
Now the muscle is in a state of relaxation
Cocking - Upon completion of the pulling mechanism, another ATP attaches to the myosin crossbridge
Preparation for another crossbridge cycle

13. Excitation-Contraction Coupling
Sequence of events that links the nerve impulse and skeletal muscle contraction
Motor Neurons – stimulates skeletal muscles
Excitatory effect
When a skeletal muscle cell receives input from a motor neuron, it depolarizes
Depolarization causes the muscle cell to fire an action potential

14. Excitation-Contraction Coupling
Action Potentials
Large changes in cell membrane potential (charge)
Inside of the cell becomes more positive relative to the outside of the cell
Function to transmit information over long distances

15. Excitation-Contraction Coupling
Neuromuscular Junction (NMJ)
The synapse between the motor neuron and the muscle cell
Synaptic Cleft
The extra-cellular space between the motor neuron and the muscle cell

17. Excitation-Contraction Coupling
The NMJ releases a neurotransmitter from the motor neuron into the synaptic cleft
The neurotransmitter is acetylcholine (ACh)
This neurotransmitter is synthesized by the nerve cell and stored in synaptic vesicles
When an nerve impulse reaches the NMJ, the synaptic vesicles release acetylcholine into the synaptic cleft.

19. Excitation-Contraction Coupling
4) Acetylcholine rapidly diffuses across the synaptic cleft to combine with receptors on muscle cell membrane (sarcolemma)
The muscle cell is also called the motor end plate membrane
5) ACh causes depolarization of the muscle cell membrane
Generates an action potential
6) Acetylcholine bound to the receptor is rapidly decomposed by acetylcholinesterase (enzyme) preventing continuous stimulation of the muscle fiber.

20. Excitation-Contraction Coupling
Stimulation of Contraction
Action potential propogates along the sarcolemma and down the T-tubules to reach the sarcoplasmic reticulum
Sarcoplasmic reticulum releases calcium
Calcium is actively pumped into and stored in the SR leaving a small concentration of calcium ions in the sarcoplasm
The action potential causes the calcium ions to be released from the SR into the sarcoplasm

21. Excitation-Contraction Coupling
When released from the SR, calcium travels toward the myofilaments
Calcium binds with troponin on the actin myofilament causing a conformational change, which results in moving tropomyosin off the active site
Myosin heads are then able to bind to the G-actin on the active sites
This begins the contraction process of crossbridge cycling

22. Excitation-Contraction Coupling
Crossbridge cycling continues as long as there is an adequate supply of ATP and if there is stimulation from a motor neuron
Crossbridge cycling stops if there is an inadequate supply of ATP or if the motor neuron impulse stops
When the motor neuron impulse stops, calcium ions are rapidly pumped back into the sarcoplasmic reticulum for storage
The calcium ion concentration in the sarcoplasm decreases
Tropomyosin returns to its original position blocking the myosin binding site on actin
The muscle cell relaxes

24. Muscle Cell Metabolism
How Muscle Cells Provide ATP to Drive the Crossbridge Cycle…
The sources of ATP:
Available ATP in the sarcoplasm
Creatine phosphate
Glucose

25. Muscle Cell Metabolism
Available ATP
There is a limited supply of readily available ATP
A small amount of ATP is stored in the myosin crossbridges immediately available when the muscle begins to contract.
Contraction uses up this source of ATP in about 6 seconds making it necessary to have other sources of ATP available

26. Muscle Cell Metabolism
Creatine Phosphate (CP)
When the ATP stores in the myosin crossbridges are exhausted, ADP and CP are used to regenerate ATP.
CP + ADP = ATP + Creatine.
The energy available from stored ATP and from the reaction of joining ADP with CP provides only about 20 seconds worth of energy
The muscles could contract only long enough to run a 100 m dash on the energy from these sources

27. Muscle Cell Metabolism
Glucose
Cellular respiration of glucose is an energy source utilized to generate ATP
Muscle contractions that are longer than seconds depend on cellular respiration of glucose as a source of ATP

28. Muscle Cell Metabolism
Recall
Cells store glucose in the sarcoplasm in the form of glycogen
The cell must break apart the glycogen molecules to release the individual glucose molecules – this is called glycogenolysis
The breakdown of glucose, called glycolysis, occurs in the sarcoplasm of the muscle cell and does not require oxygen, it is anaerobic
Glycolysis produces pyruvic acid, and a small amount of ATP.
The majority of the ATP used by muscles is formed by aerobic processes in the mitochondria.
At low intensities, the muscle cell depends on aerobic glycolysis during which oxidative phosphorylation becomes more important

29. Muscle Cell Metabolism – Changes with Exercise Intensity
Anerobic Metabolism
Oxygen is not readily available
During intense exercise, when the supply of oxygen cannot keep up with metabolic demand of the cells, pyruvic acid produced during glycolysis is converted to lactic acid.
Lactic acid accumulates in the muscle resulting in the burning sensation during short duration, high intensity muscular exercise such as lifting weights
Lactic acid is quickly removed from the muscle and taken to the liver where it is converted to glucose

30. Muscle Cell Metabolism – Changes with Exercise Intensity
Aerobic Metabolism
Oxygen is readily available
During prolonged, low-intensity exercise, the muscles are supplied with adequate oxygen by the protein myoglobin
Myoglobin
Similar to hemoglobin (oxygen binding protein in the blood)
Myoglobin has a high affinity for oxygen and binds to it loosely inside muscle cells
Myoglobin brings oxygen into the muscle cell and stores it temporarily
This provides a continuous supply of oxygen even when blood flow to the muscle is reduced

31. Muscle Cell Metabolism – Changes with Exercise Intensity
When exercise stops, the body's need for oxygen continues for a period of time
The body responds to this need by continuing to breathing heavily until all the sources of ATP have been replenished
Oxygen Debt
The amount of oxygen necessary to restore the resting metabolic state of the body
A better, and more currently accepted, term to describe the events following exercise is recovery oxygen consumption

32. Muscle Cell Metabolism – Changes with Exercise Intensity
Recovery oxygen consumption
Includes the oxygen needed to:
Restore muscles to their resting metabolic condition
Convert lactic acid to pyruvic acid in the liver
Replenish cellular stores of glycogen, creatine phosphate, and ATP
Return resting body temperature to normal
Return the heart muscle and the muscles of respiration to normal, which need repair from the minor tissue damage that occurs due to exercise
The amount of oxygen needed to meet recovery oxygen consumption demands depends on an individual's physical condition and the duration and intensity of the exercise session.

34. Types of Skeletal Muscle Fibers
Not all muscle fibers are the same physiologically
Muscles vary depending on:
The predominant pathway utilized to synthesize ATP
Oxidative fibers - predominantly aerobic pathways
Oxidative phosphorylation in the mitochondria
Fatigue-resistant fibers
Glycolytic fibers – predominantly anaerobic pathways
Glycolysis in the sarcoplasm
Fatigable fibers
The amount of myoglobin
Red fibers - high amounts of myoglobin
White fibers - small amounts of myoglobin
Efficiency of ATPase
Fast twitch fibers - decompose ATP rapidly
Slow twitch fibers - decompose ATP slowly

35. Types of Skeletal Muscle Fibers
Slow-twitch fatigue-resistant fibers
Slow oxidative fibers, or red muscle fibers.
Contain abundant myoglobin giving them their red color.
Slow acting ATPase enzymes
Abundant mitochondria
Depend upon aerobic pathways for production of ATP
Endurance type muscles
Able to deliver strong, prolonged contractions.
Examples:
Postural muscles - spinal extensors
Anti-gravity muscles - calf muscle

36. Types of Skeletal Muscle Fibers
Fast-twitch fatigable fibers
Fast glycolytic fibers, or white muscle fibers.
Contain small amounts of myoglobin
Fast acting ATPase enzymes
Allows the muscle fiber to contract rapidly
Few mitochondria
Contract for limited periods of time because fatigue rapidly
Plenty of glycogen
Depends on anaerobic metabolism
Extensive sarcoplasmic reticulum
Rapidly releases and stores calcium ions contributing to rapid contractions
Best suited for short duration, high intensity contractions

37. Types of Skeletal Muscle Fibers
Intermediate Fibers
Fast-twitch fatigue-resistant fibers
Fast glycolytic fibers
Pale muscle fibers
Characteristics lie between the red and white fibers

38. Types of Skeletal Muscle Fibers
Most of the body's muscles contain a mixture of fiber types.
It is the motor nerve that innervates the muscle cell that determines its type
Therefore, all of the muscle cells in a single motor unit are of the same type
Motor Unit – a motor neuron and all of the muscle fibers it innervates
Examples:
Running – the motor nerve stimulates the motor units containing fast-twitch fibers.
Posture – the motor nerve stimulates the motor units containing slow-twitch fibers.

39. Types of Skeletal Muscle Fibers
Slow twitch fibers are recruited first
This is because they are found in small motor units
Fast twitch fibers are recruited last
This is because they are found in large motor units

40. Types of Skeletal Muscle Fibers
People are genetically predisposed to have relatively more of one fiber type than another
People who excel at marathon running have higher percentages of slow twitch fatigue resistant muscle fibers
People who excel at sprinting have higher percentages of fast twitch fatigable fibers