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Skeletal Muscle Structure – Molecular Level

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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

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