Overview of Skeletal Muscle Tissue
Primary characteristics of muscle tissue
- Contractibility: ability to contract/shorten its length
- Excitability: responds to stimulus (including electrical, hormonal, and mechanical)
- Extensibility: ability to extend/stretch
- Elasticity: ability to recoil/return to normal shape when tension is released
Skeletal muscle anatomy review
- Muscle cell cytoplasm
- Contains high amounts of myoglobin and glycogen
- Muscle cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane
- Contain transverse tubules (T-tubules):
- Channels in the sarcolemma running from the surface of the muscle cell into the sarcoplasm and around the myofibrils
- Allow action potentials to quickly spread to the myofibrils
- Sarcoplasmic reticulum (SR):
- Specialized ER containing high levels of Ca2+
- Terminal cisternae: part of the SR that lines the T-tubules → when action potentials arrive, SR is immediately stimulated to release Ca2+ via receptors in the terminal cisternae
- Longitudinal SR: runs longitudinally along the myofilaments
Myofilaments are individual proteins that together cause muscle contraction.
- Sarcomeres: contractile structures formed by overlapping actin and myosin myofilaments
- Thick, straight filaments arranged in parallel
- Have a main shaft and a globular head on each end
- Thin filaments made of 2 long-coiling protein strands
- Connected to each other at the Z line of sarcomeres
- Located between each myosin filament
- Regulatory proteins:
- Regulate binding of actin to myosin
- Tropomyosin: a ropelike protein covering the myosin-binding sites on actin
- Troponin C (TnC): contains binding sites for Ca2+
- Troponin I (TnI): inhibits actin and myosin binding
- Troponin T (TnT): connects the other troponins to tropomyosin
Review of sarcomere structure
The myofibrils are organized in a pattern that creates different bands and zones when viewed under microscopy. These bands are created by overlapping actin and myosin strands.
- Z line (also called the Z band or Z disc):
- Anchors and separates 1 sarcomere from another
- A sarcomere is defined as the region between 2 Z lines
- Anisotropic bands (A bands):
- Dark bands on microscopy → memory trick: “dark” has an “A” in it
- Formed by entire length of thick myosin filaments, which includes overlapping actin filaments at the ends
- Isotropic bands (I bands):
- Light bands on microscopy → memory trick: “light” has an “I” in it
- Consist of only thin actin filaments
- I bands are between the A bands and include the Z line.
- H zone:
- Lighter zone in the middle of the A Band
- Consists of only myosin filaments → excludes the ends of the myosin which are overlapping with actin
- M bands:
- Fine, dark line in the center of the H zone
- Myosin-binding proteins attach here
Innervation of Skeletal Muscle Fibers
Skeletal muscle cell contraction requires stimulation by an action potential from somatic motor neurons.
The neuromuscular junction (NMJ)
- Also called an end plate
- A synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission (i.e., connection) between a skeletal muscle cell and motor neuron
- Each skeletal muscle cell (i.e., muscle fiber) has 1 NMJ around the midpoint of the cell.
- Synaptic knob: a swelling at the end of the motor neuron
- Motor end plate: depression in the sarcolemma of the adjacent muscle fiber, in close association with the synaptic knob
- Synaptic cleft: the space between the synaptic knob and the motor end plate
- Schwann cell: specialized cell that surrounds and protects the NMJ
Process of transmitting a neuronal signal to the muscle cell
- Acetylcholine (ACh) is released from synaptic vesicles in the synaptic knob.
- ACh crosses the synaptic cleft.
- ACh binds to and activates receptors on the motor end plate (there are approximately 50 million ACh receptors per NMJ)
- Acetylcholinesterase (AChE): breaks down ACh left in the synaptic cleft to “turn off” the signal
- A group of muscle fibers working together that are controlled by a single motor neuron
- Small motor units:
- Only a few muscle fibers per neuron
- Allows for fine muscle control
- Example: eye muscles
- Large motor units:
- Up to several hundred muscle fibers innervated by a single neuron
- Example: large postural muscles
How an Individual Muscle Fiber Contracts
- A nerve signal arrives at the synaptic knob.
- Voltage-gated Ca channels open, stimulating the release of ACh into the synaptic cleft.
- ACh binds to and activates ligand-gated ion channels on the motor end plate of the muscle fiber.
- Allows Na+ into the muscle cell
- Allows K+ out of the cell
- This flow of ions reverses the polarity of the sarcolemma = depolarization
- Depolarization triggers nearby voltage-gated Na+ and K+ channels to open, causing depolarization in these areas → creates a wave of depolarization known as an action potential (AP)
- The AP propagates in all directions throughout the sarcolemma, including down the T-tubules.
- The AP stimulates voltage-dependent dihydropyridine (DHP) receptors:
- Membrane-bound receptors lining the T-tubules
- Mechanically tethered to ryanodine receptors, which sit on (and keep closed) the Ca-release channels in the SR under resting conditions
- Stimulation of the DHP receptors move the ryanodine receptors → opening the Ca-release channels in the SR
- Ca2+ ions flood out of the SR into the sarcoplasm → bind to troponins on the thin filaments (actin)
- The troponin–tropomyosin complex changes shape → shifts to a new position, allowing actin and myosin to bind
Crossbridge cycling is the process by which the myosin and actin move along each other, shortening the sarcomere and causing muscle contraction. This process is also known as the sliding filament theory of muscle contraction.
- ATP binds the myosin head.
- Myosin ATPase hydrolyzes the ATP → ADP:
- Moves the myosin head into a high-energy “cocked” position
- This movement is known as the recovery stroke.
- The cocked myosin head binds an exposed binding site on actin, forming a crossbridge. Note: Ca must be present and bound to troponin in order for the myosin-binding sites on actin to be uncovered and available.
- Power stroke:
- Myosin releases the ADP and phosphate.
- Myosin head expels the energy → returns to the flexed position, pulling the thin filament with it
- Since many myosin heads are bound simultaneously, the thin filament remains in its new position rather than “slipping back” to its original position.
- Power strokes shorten the I band and moves Z lines closer together:
- → Sarcomeres shorten and move closer together
- → Muscle fibers shorten
- → Entire muscle shortens, generating movement
- Note that the myofilaments themselves do not shorten; they simply overlap more.
- Note that the A band also does not shorten, though A bands do move closer together.
- Myosin binds a new ATP, causing it to release from the actin.
- The cycle starts over.
- The motor neuron ceases, sending its chemical signal, ACh, into the synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission at the NMJ.
- ACh in the synaptic cleft is broken down by AChE.
- The sarcolemma repolarizes.
- Ryanodine receptors close the Ca-release channels on the SR, preventing further Ca2+ efflux.
- Sarco-/endoplasmic reticulum Ca-ATPase (SERCA): pumps Ca back into the SR, removing it from the sarcoplasm
- Calsequestrin: binds Ca2+ within the SR, which stores/sequesters it until a new signal for muscle contraction arrives
- Without Ca2+, the troponin–tropomyosin complex shifts, covering the binding sites on actin.
- Myosin can no longer bind actin, and the sarcomere relaxes.
Generating Force During Muscle Contractions
The length–tension relationship
The resting length of the sarcomere has a direct influence on the force generated when the sarcomere shortens. This is called the length–tension relationship.
- Active tension: the tension produced by power strokes
- The amount of tension that can be actively produced is dependent on the starting length of the sarcomere.
- Overcontracted at rest (i.e., shorter starting length):
- The ends of the thick filaments are close to Z lines.
- Minimal room for them to contract further
- → A weak contraction before the fiber runs out of room to contract
- Overstretched at rest (i.e., longer starting length):
- Minimal overlap between actin and myosin
- Fewer myosin heads can come in contact with the actin.
- → Weaker initial contraction
- Optimal resting length:
- The length at which a muscle can produce the greatest force when it contracts
- Controlled by the CNS
- Muscle tone: state of partial contraction that is maintained by the CNS under resting conditions, generating the optimal resting length
- Passive tension: tension that resists the myofilaments being pulled apart
- Total muscle tension: equals active tension plus passive tension
Threshold, latent periods, and twitch
- Threshold: minimum voltage necessary to generate an AP (an all-or-none response)
- Latent period:
- The time between onset of the AP and onset of the muscle contraction (i.e., the twitch)
- During this time, excitation–contraction coupling is occurring:
- The AP is being propagated through the sarcolemma.
- DHP receptors are activated.
- Ca ions are released from the SR.
- No increase in tension during the latent period
- Typically lasts approximately 2 milliseconds
- An isolated, rapid contraction followed by rapid relaxation
- Typically lasts approximately 5‒100 milliseconds
- Contraction phase:
- Occurs during crossbridge cycling
- Tension increases throughout this phase until peak tension is reached.
- Relaxation phase,
- Contraction ends and tension decreases.
- Ca2+ ions are pumped back into the SR → without Ca2+, crossbridge formation cannot occur → muscle fibers return to their resting state
Coordinating twitches so that muscles can do meaningful work
A single isolated twitch of a single muscle fiber cannot do meaningful work, and increasing the voltage of the stimulus does not increase the strength of a twitch. Ways to increase the strength of a muscle contraction include:
- Recruitment (also called multiple motor unit summation): increasing the voltage stimulus to the motor neuron itself excites more nerve fibers → excites more motor units
- ↑ Frequency of stimulation:
- Repetitive stimulation → increases tension with each twitch because:
- The SR cannot fully recover all of the Ca2+ between twitches
- Twitches produce heat → heat causes myosin ATPase to work more efficiently
- If twitches cannot fully recover before the next twitch starts, tension increases (known as temporal summation or wave summation)
- At > 40 stimuli per second:
- Muscle has no time to relax at all.
- Muscle goes into a sustained prolonged contraction known as tetanus Tetanus Tetanus is a bacterial infection caused by Clostridium tetani, a gram-positive obligate anaerobic bacterium commonly found in soil that enters the body through a contaminated wound. C. tetani produces a neurotoxin that blocks the release of inhibitory neurotransmitters and causes prolonged tonic muscle contractions. Tetanus.
- Tetanus does not occur in the body under normal physiologic conditions.
- Repetitive stimulation → increases tension with each twitch because:
- Motor units function asynchronously:
- When 1 motor unit relaxes, another takes over.
- Allows for “smooth” muscle contractions in which the muscle as a whole does not lose tension
Types of skeletal muscle contraction
There are multiple types of muscle contraction based on how the muscle fiber changes length during the contraction:
- A muscular contraction in which the length of the muscle does not change
- Example: holding a plank position
- Maintain constant tension in the muscle as the muscle changes length
- Example: bicep curls
- Have concentric and eccentric phases
- Shortening of the sarcomere, muscle fiber, and muscle, generating limb movement
- E.g., lifting a weight during a bicep curl
- Lengthening the muscle while still contracting (i.e., generating force)
- Occurs when the resistance against the muscle is greater than the force generated
- E.g., lowering a bicep curl
- Auxotonic contraction:
- Simultaneous changes in both muscle tension and length
- I.e., a combination of isometric and isotonic contractions
- Most regular movements are auxotonic.
Energy Sources and Types of Muscle Fibers
Adenosine triphosphate is the primary energy source required to generate the power strokes causing muscle contraction. There are several different ways this ATP energy is generated, and there are several different types of muscle fibers based on their capacity to use different energy sources.
Adenosine triphosphate concentration in the muscle fiber is only enough to sustain full contraction for 1 to 2 seconds. Therefore, ADP must be rephosphorylated to generate new ATP, allowing the muscle to continue contracting, which requires energy.
- For immediate energy:
- Phosphagen system:
- Creatine phosphate: an energy-storage molecule that can donate a phosphate group to ADP
- CK: transfers the phosphate group from creatine phosphate to ADP → ATP
- The phosphagen system provides nearly all the energy used in short bursts of intense activity.
- Myokinase: can transfer a phosphate group from 1 ADP to another, creating an ATP
- Phosphagen system:
- For short-term energy: anaerobic fermentation
- Takes over as the phosphagen system is exhausted
- Glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis: converts glycogen → lactic acid, generating ATP in the process
- Produces enough ATP to sustain activity for about 30–40 seconds
- Lactic acid (toxic) builds up → major factor in muscle fatigue
- For long-term energy: aerobic respiration
- The major source of energy for activity lasting longer than approximately 30‒40 seconds
- Requires O2
- Occurs once cardiovascular changes have “caught up” with the increase in activity level and blood flow is now delivering enough O2 for aerobic respiration to occur
- Fatty acids and glucose are used to generate ATP through the Krebs cycle and oxidative phosphorylation (i.e., the electron transport chain Electron transport chain The electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP). Electron Transport Chain (ETC) (ETC))
- Aerobic respiration continues until endurance is depleted via:
- ↓ Glycogen and blood glucose (BG)
- Loss of fluid and electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes through sweating
- These energy sources are not used one at a time. Mechanisms blend as exercise continues.
Types of skeletal muscle fibers
There are 3 primary types of skeletal muscle fibers, found in different muscles throughout the body based on their function.
Type I fibers: slow-twitch muscle fibers
- Slow oxidative fibers
- Fatigue-resistant motor units
- Examples of activities that require the use of slow oxidative fibers:
- Back muscles used to maintain posture
- Running a marathon
Type II fibers: fast-twitch muscle fibers
- Type IIA:
- Fast oxidative glycolytic fibers
- Fatigue resistant
- Used in movement that requires higher sustained power
- Example of activity using fast oxidative glycolytic fibers: 800-meter race
- Type IIB:
- Fast glycolytic fibers
- Store large amounts of glycogen
- Fatigue-prone due to buildup of lactic acid during use
- Examples of activities using fast glycolytic fibers:
- Shot put
- Long jump
- 100-meter dash
|SO/Type I||FOG/Type IIA||FOG/Type IIB|
|Myosin ATPase activity||Slow||Fast||Fast|
|Fatigue resistance capacity||High||Moderate||Low|
FG: fast glycolytic
FOG: fast oxidative glycolytic
- Duchenne muscular dystrophy Duchenne muscular dystrophy Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder that is caused by a mutation in the DMD gene. The mutation leads to the production of abnormal dystrophin, resulting in muscle-fiber destruction and replacement with fatty or fibrous tissue. Duchenne Muscular Dystrophy (DMD): an X-linked recessive genetic disorder that is caused by a mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in the DMD gene. The mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations leads to the production of abnormal dystrophin, resulting in muscle-fiber destruction and replacement with fatty and fibrous tissue. Affected individuals present with progressive proximal muscle weakness leading to the eventual loss of ambulation, as well as contractures, scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis, cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Overview of Cardiomyopathies (CM), and respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure.
- Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis (MG): an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction and/or destruction of ACh receptors at the NMJ. Individuals present with fatigue, ptosis, diplopia, dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming "stuck." Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis can progress to a life-threatening cholinergic crisis with respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure, but prognosis is generally good with treatment.
- Spastic paralysis: a state of continued contraction, which can cause suffocation if the laryngeal and/or respiratory muscles are affected, and can be caused by cholinesterase inhibitors, a toxin found in some pesticides. Such toxins block the function of AChE, the enzyme normally responsible for breaking down ACh in the NMJ. Blocking degradation of ACh leads to sustained contractions. Individuals should be kept lying down and calm.
- Dystonia Dystonia Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia: a movement disorder characterized by sustained or intermittent muscle contractions causing involuntary movements, twisting, and/or fixed postures. The disorder may be hereditary, idiopathic, or acquired, and it can be classified into focal, multifocal, segmental, or generalized dystonia based on anatomical involvement. Treatment involves pharmacologic management with levodopa, anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs agents, and/or botulinum toxin.
- Electromyography (EMG): a diagnostic procedure that assesses muscle activation in response to neuronal activity. The procedure is employed to differentiate between neuropathic and myopathic muscle weakness, determine the extent of nerve damage, and localize neural injury.
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