Skeletal Muscle Contraction

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 Recoil Vessels can stretch and return to their original shape after receiving the stroke volume of blood ejected by the left ventricle during systole. Arteries: Histology/return to normal shape when tension is released

Skeletal muscle anatomy review

• Sarcoplasm Sarcoplasm Muscle Tissue: Histology: 
  • Muscle cell cytoplasm
  • Contains high amounts of myoglobin Myoglobin A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. Rhabdomyolysis and glycogen
• Sarcolemma Sarcolemma The excitable plasma membrane of a muscle cell. Muscle Tissue: Histology: 
  • 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 Channels The Cell: Cell Membrane in the sarcolemma Sarcolemma The excitable plasma membrane of a muscle cell. Muscle Tissue: Histology running from the surface of the muscle cell into the sarcoplasm Sarcoplasm Muscle Tissue: Histology and around the myofibrils Myofibrils The long cylindrical contractile organelles of striated muscle cells composed of actin filaments; myosin filaments; and other proteins organized in arrays of repeating units called sarcomeres. Muscle Tissue: Histology
    • Allow action potentials to quickly spread to the myofibrils Myofibrils The long cylindrical contractile organelles of striated muscle cells composed of actin filaments; myosin filaments; and other proteins organized in arrays of repeating units called sarcomeres. Muscle Tissue: Histology
• Sarcoplasmic reticulum Sarcoplasmic Reticulum A network of tubules and sacs in the cytoplasm of skeletal muscle fibers that assist with muscle contraction and relaxation by releasing and storing calcium ions. Muscle Tissue: Histology (SR): 
  • Specialized ER containing high levels of Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ 
  • Terminal cisternae: part of the SR that lines the T-tubules → when action potentials arrive, SR is immediately stimulated to release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ via receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors in the terminal cisternae
  • Longitudinal SR: runs longitudinally along the myofilaments Myofilaments Refers to individual proteins that together cause muscle contraction. Muscle Tissue: Histology

Myofilaments Myofilaments Refers to individual proteins that together cause muscle contraction. Muscle Tissue: Histology

Myofilaments Myofilaments Refers to individual proteins that together cause muscle contraction. Muscle Tissue: Histology are individual proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis that together cause muscle contraction. 

• Sarcomeres: contractile structures formed by overlapping actin and myosin myofilaments Myofilaments Refers to individual proteins that together cause muscle contraction. Muscle Tissue: Histology
• Myosin: 
  • Thick, straight filaments arranged in parallel
  • Have a main shaft and a globular head on each end
• Actin: 
  • 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 Regulatory proteins Proteins and Peptides:
  • Regulate binding of actin to myosin 
  • Tropomyosin: a ropelike protein covering the myosin-binding sites on actin
  • Troponin: 
    • Troponin C (TnC): contains binding sites for Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺
    • Troponin I Troponin I A troponin complex subunit that inhibits actomyosin ATPase activity thereby disrupting actin and myosin interaction. There are three troponin I subtypes: troponin i1, i2 and i3. Troponin i3 is cardiac-specific whereas troponin i1 and i2 are skeletal subtypes. Troponin i3 is a biomarker for damaged or injured cardiac myocytes and mutations in troponin i3 gene are associated with familial hypertrophic cardiomyopathy. Myocardial Infarction (TnI): inhibits actin and myosin binding
    • Troponin T (TnT): connects the other troponins to tropomyosin

Review of sarcomere Sarcomere The repeating contractile units of the myofibril, delimited by z bands along its length. Muscle Tissue: Histology structure

The myofibrils Myofibrils The long cylindrical contractile organelles of striated muscle cells composed of actin filaments; myosin filaments; and other proteins organized in arrays of repeating units called sarcomeres. Muscle Tissue: Histology 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 Actin filaments Fibers composed of microfilament proteins, which are predominately actin. They are the smallest of the cytoskeletal filaments. The Cell: Cytosol and Cytoskeleton
  • 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 Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis attach here

Innervation of Skeletal Muscle Fibers

Skeletal muscle cell contraction requires stimulation by an action potential Action Potential Abrupt changes in the membrane potential that sweep along the cell membrane of excitable cells in response to excitation stimuli. Membrane Potential from somatic motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology.

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 Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neuron
• Each skeletal muscle cell (i.e., muscle fiber) has 1 NMJ around the midpoint of the cell.
• Synaptic knob: a swelling Swelling Inflammation at the end of the motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neuron
• Motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology end plate: depression in the sarcolemma Sarcolemma The excitable plasma membrane of a muscle cell. Muscle Tissue: Histology of the adjacent muscle fiber, in close association with the synaptic knob
• Synaptic cleft Synaptic cleft Synapses and Neurotransmission: the space between the synaptic knob and the motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology end plate
• Schwann cell Schwann Cell Neuroglial cells of the peripheral nervous system which form the insulating myelin sheaths of peripheral axons. Nervous System: Histology: specialized cell that surrounds and protects the NMJ

Process of transmitting a neuronal signal to the muscle cell

• Acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS ( ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS) is released from synaptic vesicles Vesicles Female Genitourinary Examination in the synaptic knob.
• ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS crosses the synaptic cleft Synaptic cleft Synapses and Neurotransmission.
• ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS binds to and activates receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors on the motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology end plate (there are approximately 50 million ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors per NMJ)
• Acetylcholinesterase (AChE): breaks down ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS left in the synaptic cleft Synaptic cleft Synapses and Neurotransmission to “turn off” the signal

Motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology units

• A group of muscle fibers working together that are controlled by a single motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neuron
• Small motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology units:
  • Only a few muscle fibers per neuron
  • Allows for fine muscle control
  • Example: eye muscles
• Large motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology units:
  • Up to several hundred muscle fibers innervated by a single neuron
  • Example: large postural muscles

How an Individual Muscle Fiber Contracts

Excitation

• A nerve signal arrives at the synaptic knob.
• Voltage-gated Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts) channels Channels The Cell: Cell Membrane open, stimulating the release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS into the synaptic cleft Synaptic cleft Synapses and Neurotransmission.
• ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS binds to and activates ligand-gated ion channels Channels The Cell: Cell Membrane on the motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology end plate of the muscle fiber.
  • Allows Na⁺ into the muscle cell 
  • Allows K⁺ out of the cell
• This flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure of ions reverses the polarity of the sarcolemma Sarcolemma The excitable plasma membrane of a muscle cell. Muscle Tissue: Histology = depolarization Depolarization Membrane Potential
• Depolarization Depolarization Membrane Potential triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) nearby voltage-gated Na⁺ and K⁺ channels Channels The Cell: Cell Membrane to open, causing depolarization Depolarization Membrane Potential in these areas → creates a wave A wave Cardiac Cycle of depolarization Depolarization Membrane Potential known as an action potential Action Potential Abrupt changes in the membrane potential that sweep along the cell membrane of excitable cells in response to excitation stimuli. Membrane Potential (AP)
• The AP propagates in all directions throughout the sarcolemma Sarcolemma The excitable plasma membrane of a muscle cell. Muscle Tissue: Histology, including down the T-tubules.

Excitation-contraction coupling

• The AP stimulates voltage-dependent dihydropyridine Dihydropyridine Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers) (DHP) receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors:
  • Membrane-bound receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors lining the T-tubules
  • Mechanically tethered to ryanodine receptors Ryanodine Receptors Malignant Hyperthermia, which sit on (and keep closed) the Ca-release channels Channels The Cell: Cell Membrane in the SR under resting conditions
  • Stimulation of the DHP receptors DHP receptors Malignant Hyperthermia move the ryanodine receptors Ryanodine Receptors Malignant Hyperthermia → opening the Ca-release channels Channels The Cell: Cell Membrane in the SR
• Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ ions flood out of the SR into the sarcoplasm Sarcoplasm Muscle Tissue: Histology → bind BIND Hyperbilirubinemia of the Newborn to troponins on the thin filaments (actin)
• The troponin–tropomyosin complex changes shape → shifts to a new position, allowing actin and myosin to bind BIND Hyperbilirubinemia of the Newborn

Crossbridge cycling Crossbridge cycling Smooth Muscle Contraction

Crossbridge cycling Crossbridge cycling Smooth Muscle Contraction is the process by which the myosin and actin move along each other, shortening the sarcomere Sarcomere The repeating contractile units of the myofibril, delimited by z bands along its length. Muscle Tissue: Histology and causing muscle contraction. This process is also known as the sliding filament theory of muscle contraction Sliding filament theory of muscle contraction Smooth 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 CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts) 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 Phosphate Inorganic salts of phosphoric acid. Electrolytes.
  • 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 Myofilaments Refers to individual proteins that together cause muscle contraction. Muscle Tissue: Histology 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 Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology from the actin.
• The cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation starts over.

Relaxation

• The motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neuron ceases, sending its chemical signal, ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS, 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 ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS in the synaptic cleft Synaptic cleft Synapses and Neurotransmission is broken down by AChE.
• The sarcolemma Sarcolemma The excitable plasma membrane of a muscle cell. Muscle Tissue: Histology repolarizes.
• Ryanodine receptors Ryanodine Receptors Malignant Hyperthermia close the Ca-release channels Channels The Cell: Cell Membrane on the SR, preventing further Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ efflux.
• Sarco-/ endoplasmic reticulum Endoplasmic reticulum A system of cisternae in the cytoplasm of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (cell membrane) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced; otherwise it is said to be smooth-surfaced. The Cell: Organelles Ca-ATPase (SERCA): pumps Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts) back into the SR, removing it from the sarcoplasm Sarcoplasm Muscle Tissue: Histology
• Calsequestrin: binds Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ within the SR, which stores/sequesters it until a new signal for muscle contraction arrives
• Without Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺, the troponin–tropomyosin complex shifts, covering the binding sites on actin.
• Myosin can no longer bind BIND Hyperbilirubinemia of the Newborn actin, and the sarcomere Sarcomere The repeating contractile units of the myofibril, delimited by z bands along its length. Muscle Tissue: Histology relaxes.

Generating Force During Muscle Contractions

The length–tension relationship Relationship A connection, association, or involvement between 2 or more parties. Clinician–Patient Relationship

The resting length of the sarcomere Sarcomere The repeating contractile units of the myofibril, delimited by z bands along its length. Muscle Tissue: Histology has a direct influence on the force generated when the sarcomere Sarcomere The repeating contractile units of the myofibril, delimited by z bands along its length. Muscle Tissue: Histology shortens. This is called the length–tension relationship Relationship A connection, association, or involvement between 2 or more parties. Clinician–Patient 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 Sarcomere The repeating contractile units of the myofibril, delimited by z bands along its length. Muscle Tissue: Histology.
  • 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 Myofilaments Refers to individual proteins that together cause muscle contraction. Muscle Tissue: Histology 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 Sarcolemma The excitable plasma membrane of a muscle cell. Muscle Tissue: Histology.
    • DHP receptors DHP receptors Malignant Hyperthermia are activated.
    • Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts) ions are released from the SR.
  • No increase in tension during the latent period
  • Typically lasts approximately 2 milliseconds
• Twitch: 
  • An isolated, rapid contraction followed by rapid relaxation 
  • Typically lasts approximately 5‒100 milliseconds 
  • Contraction phase:
    • Occurs during crossbridge cycling Crossbridge cycling Smooth Muscle Contraction
    • Tension increases throughout this phase until peak tension is reached.
  • Relaxation phase,
    • Contraction ends and tension decreases.
    • Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ ions are pumped back into the SR → without Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺, 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 Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology unit summation): increasing the voltage stimulus to the motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neuron itself excites more nerve fibers Nerve Fibers Slender processes of neurons, including the axons and their glial envelopes (myelin sheath). Nerve fibers conduct nerve impulses to and from the central nervous system. Nervous System: Histology → excites more motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology units
• ↑ Frequency of stimulation:
  • Repetitive stimulation → increases tension with each twitch because:
    • The SR cannot fully recover all of the Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ between twitches
    • Twitches produce heat Heat Inflammation → heat Heat Inflammation 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 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 does not occur in the body under normal physiologic conditions.
• Motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology units function asynchronously:
  • When 1 motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology 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:

• Isometric: 
  • A muscular contraction in which the length of the muscle does not change
  • Example: holding a plank position
• Isotonic Isotonic Solutions having the same osmotic pressure as blood serum, or another solution with which they are compared. Renal Sodium and Water Regulation:
  • Maintain constant tension in the muscle as the muscle changes length 
  • Example: bicep curls
  • Have concentric and eccentric phases
  • Concentric: 
    • Shortening of the sarcomere Sarcomere The repeating contractile units of the myofibril, delimited by z bands along its length. Muscle Tissue: Histology, muscle fiber, and muscle, generating limb movement 
    • E.g., lifting a weight during a bicep curl
  • Eccentric: 
    • Lengthening the muscle while still contracting (i.e., generating force)
    • Occurs when the resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing 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 Isotonic Solutions having the same osmotic pressure as blood serum, or another solution with which they are compared. Renal Sodium and Water Regulation contractions
  • Most regular Regular Insulin movements are auxotonic.

Energy Sources and Types of Muscle Fibers

Adenosine Adenosine A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Class 5 Antiarrhythmic Drugs 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.

Energy sources

Adenosine Adenosine A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Class 5 Antiarrhythmic Drugs 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 Creatine An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. Acute Kidney Injury phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes: an energy-storage molecule that can donate a phosphate group Phosphate group Nucleic Acids to ADP
    • CK: transfers the phosphate group Phosphate group Nucleic Acids from creatine Creatine An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. Acute Kidney Injury phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes to ADP → ATP
    • The phosphagen system provides nearly all the energy used in short bursts of intense activity.
  • Myokinase: can transfer a phosphate group Phosphate group Nucleic Acids from 1 ADP to another, creating an ATP
• 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 Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
• For long-term energy: aerobic respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose Anatomy (External & Internal) 
  • 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 Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure is now delivering enough O₂ for aerobic respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose Anatomy (External & Internal) to occur
  • Fatty acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance and glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance are used to generate ATP through the Krebs cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation and oxidative phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing (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 ETC 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)))
  • Aerobic respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose Anatomy (External & Internal) continues until endurance is depleted via:
    • ↓ Glycogen and blood glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance (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 Type I fibers Skeletal muscle fibers characterized by their expression of the type I myosin heavy chain isoforms which have low ATPase activity and effect several other functional properties – shortening velocity, power output, rate of tension redevelopment. Muscle Tissue: Histology: slow-twitch muscle fibers Slow-twitch muscle fibers Skeletal muscle fibers characterized by their expression of the type I myosin heavy chain isoforms which have low ATPase activity and effect several other functional properties – shortening velocity, power output, rate of tension redevelopment. Energy Homeostasis

• Slow oxidative fibers
• Fatigue-resistant motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology units
• Examples of activities that require the use of slow oxidative fibers:
  • Back muscles Back muscles The back is composed of several muscles of varying sizes and functions, which are grouped into intrinsic (or primary) back muscles and extrinsic (or secondary) back muscles. The extrinsic muscles comprise the superficial and intermediate muscle groups, while the intrinsic muscles comprise the deep muscles. Muscles of the Back: Anatomy used to maintain posture
  • Running a marathon

Type II fibers Type II fibers Skeletal muscle fibers characterized by their expression of the type II myosin heavy chain isoforms which have high ATPase activity and effect several other functional properties – shortening velocity, power output, rate of tension redevelopment. Several fast types have been identified. Muscle Tissue: Histology: fast-twitch muscle fibers Fast-twitch muscle fibers Skeletal muscle fibers characterized by their expression of the type II myosin heavy chain isoforms which have high ATPase activity and effect several other functional properties – shortening velocity, power output, rate of tension redevelopment. Several fast types have been identified. Energy Homeostasis

• Type IIA:
  • Fast oxidative glycolytic fibers
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia 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

Clinical Relevance

• Duchenne muscular dystrophy Muscular Dystrophy Becker Muscular Dystrophy ( DMD DMD 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): an X-linked recessive X-Linked Recessive Duchenne Muscular Dystrophy 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 DMD gene Duchenne Muscular Dystrophy. 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 Dystrophin A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. Blotting Techniques, resulting in muscle-fiber destruction and replacement with fatty and fibrous Fibrous Fibrocystic Change tissue. Affected individuals present with progressive proximal muscle weakness Proximal Muscle Weakness Lambert-Eaton Myasthenic Syndrome leading to the eventual loss of ambulation, as well as contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing, 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). Cardiomyopathy: Overview and Types (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 Skeletal muscles A subtype of striated muscle, attached by tendons to the skeleton. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles. Muscle Tissue: Histology caused by dysfunction and/or destruction of ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors at the NMJ. Individuals present with fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, ptosis Ptosis Cranial Nerve Palsies, diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis, 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 Cholinergic Crisis Myasthenia Gravis 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 Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas 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 Cholinesterase Liver Function Tests inhibitors, a toxin found in some pesticides. Such toxins block the function of AChE, the enzyme normally responsible for breaking down ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS in the NMJ. Blocking degradation of ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS 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 Idiopathic Dermatomyositis, or acquired, and it can be classified into focal, multifocal Multifocal Retinoblastoma, segmental, or generalized dystonia Generalized Dystonia Dystonia based on anatomical involvement. Treatment involves pharmacologic management with levodopa Levodopa The naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonian disorders and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. Parkinson’s Disease Drugs, 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 Botulinum toxin Toxic proteins produced from the species Clostridium botulinum. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon endocytosis into presynaptic nerve endings. Once inside the cell the botulinum toxin light chain cleaves specific snare proteins which are essential for secretion of acetylcholine by synaptic vesicles. This inhibition of acetylcholine release results in muscular paralysis. Botulism.
• Electromyography Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Becker Muscular Dystrophy (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.