Skeletal Muscle Function and Characteristics

• There are over 600 named skeletal muscles in the body
• Each skeletal muscle is a discrete organ

Skeletal Muscle Function

• Produces movement via physical movement (locomotion)
• Gives protection and support and holds internal organs in place
• Maintains posture and stabilizes joints
• Muscles generate heat by converting energy into heat energy as they work
• Facilitates interpersonal communication through speaking, facial expressions, and gestures
• Enables typing and writing

Characteristics of Muscles

• Contractility: Muscles forcibly shorten when stimulated
• Excitability: Exhibit the ability to receive and respond to a chemical stimulus
• Extensibility: Can stretch beyond their resting length
• Elasticity: Ability to recoil and resume their resting length
• Plasticity: Constantly adapt based on usage

Connective Tissue Components

• Supports and reinforces the whole muscle acting as a unit
• There are three concentric layers of connective tissue: Epimysium, Perimysium, and Endomysium
• Epimysium surrounds the whole muscle
• Perimysium surrounds bundles of muscle fibers, the surrounded unit is called a fascicle
• Endomysium surrounds the individual muscle fiber
• Tendons are thick cordlike structures of dense regular CT
• Attach muscle to bone, skin or muscle
• Formed by the convergence of the three concentric layers extending beyond the muscle fibers and attaching to the periosteum

Microanatomy of Skeletal Muscle

• Sarcolemma: The plasma membrane of the muscle fiber
• Sarcoplasm: Cytoplasm of the muscle cell
• Sarcoplasm contains several glycosomes (stored glycogen granules), myoglobin to store O2 and a high concentration of mitochondria
• Muscle contains multiple nuclei
• Triad contains Transverse tubules (T-tubules) and Sarcoplasmic reticulum (SR)
• Transverse tubules (T-tubules) are membranous tubes that travel perpendicular to the length of the fiber
• T Tubules allow for the conduction of an action potential from the surface of the cell through it
• Sarcoplasmic reticulum (SR) is a modified endoplasmic reticulum surrounding each myofibril
• Sarcoplasmic reticulum stores high concentrations of [Ca2+] that when released facilitate a muscle contraction
• Terminal Cisternae, blind ended sacs at the end of the SR adjacent to T-tubules, serve as the reservoir for [Ca2+]

Myofibril Organization

• Myofibrils are highly organized cytoskeletons, where 100s to 1000s are found in a cell, extending the entire length of the cell
• Are composed of myofilaments
• Thick filaments are an assemblage of myosin (protein with 2 identical subunits, intertwined long tails & 2 globular heads)
• Two halves: myosin is oriented in opposing directions with the heads facing outward, with heads responsible for the cross-bridges
• Heads have two functional sites which are Actin-binding Site and ATPase Site
• Thin filaments are assemblage of actin
• F-Actin contain two strands of G-actin molecules forming a helix that has functional binding sites for myosin
• Tropomyosin are long chains that bind to actin and "hides" the myosin binding site
• Troponin bridges tropomyosin and actin and binds to Ca2+

Sarcomere Organization

• Sarcomere is the functional unit of the muscle which increases in length by adding more sarcomeres not by increasing the length of a sarcomere
• It is the area between two Z lines (cytoskeletal disc that interconnects the actin filaments)
• I band constitutes the portion of the thin filaments that do not project into the A band
• I bands project from the Z lines
• A band is the region of thick filaments and the overlapping thin filament
• H zone lies within the A band, consists of thick filaments only
• M line contains transverse proteins that interconnect the thick filaments, extends vertically down the middle of the A band at the center of the H zone

Additional Structural Proteins

• Nebulin is an inelastic protein that helps align actin filaments and is attached to the Z disks
• Titin is a single-stranded elastic protein that extends along the length of the thick filament from the M line to the Z line
• Titin acts as a spring to passively recoil the muscle cell to its resting length after a stretch and helps stabilize the position of the thick filament
• Dystrophin is a protein complex that anchors myofibrils near the sarcolemma to the sarcolemma
• α actinin crosslinks antiparallel thin filaments

Motor Unit

• Consists of a single alpha motor neuron and the muscle fibers it innervates
• The number of fibers in a motor unit varies depending on the action performed by that muscle
• Delicate activity requires few muscle fibers/motor unit
• Coarse activity requires many muscle fibers/motor unit
• Fibers in a motor unit are not clustered but dispersed throughout a muscle
• Stimulation of a motor unit results in an evenly distributed contraction (twitch)

Neuromuscular Junction

• Each skeletal muscle has one and is the point where the innervating neuron interacts with the muscle fiber
• Synaptic knob is the terminal end of the motor neuron's axon which houses synaptic vesicles containing the neurotransmitter acetylcholine (ACh)
• Motor end plate represents a specialized region of the sarcolemma underlying the synaptic knob and it has ACh receptors that are chemically gated ion channels
• Synaptic cleft is the space lying between the synaptic knob and motor end plate, containing Acetylcholinesterase (AChE) which breaks down ACh to clear the signal

The Muscle Twitch Phenomenon

• Twitch: A simple brief contraction in a muscle fiber
• Latent period is the time delay between stimulation and the beginning of the contraction
• Contraction time represents onset of contraction to the peak of tension
• Relaxation time represents period from peak of tension to rest
• Stimulation of a muscle fiber produces a twitch which is too weak and short to be of use
• Cooperative and additive twitches can add up to a functional muscle contraction

Steps in Muscle Contraction

• Neuromuscular junction excitation starts in a skeletal fiber with the release of neurotransmitter acetycholine (ACh) from synaptic vesicles
• Released ACh binds to ACh receptors
• Binding triggers propagation of an action potential along the sarcolemma and T-tubules to the sarcoplasmic reticulum
• Sarcoplasmic reticulum is stimulated to release Ca2+
• Released Ca2+ binds to troponin which triggers sliding of thin filaments past thick filaments of sarcomeres causing a muscle contraction

Initiation of Muscle Contraction

• Action potential arrives at synaptic knob of motor neuron
• Leads to Ca2+ entry at synaptic knob
• Triggers release of ACh from synaptic knob
• ACh binds receptor on muscle cell which leads to Na+ rushing into cell
• In-rushing Na+ leads to an end-plate potential and then initiation and propagation of action potential
• Action potential travels along length of cell and down through T-tubules

Role of Additional Channels in Muscle Contraction

• Action potential moves down through T-tubules and triggers opening DHP channels
• DHP Channels are Voltage-gated L-type Ca2+ channels, associated with RyR channels
• Opening of DHP channels leads to opening of RyR channels (on the SR)
• RyR channels are located on the SR and allow a final outflow of Ca2+ into the cytoplasm

Crossbridge Formation

• Ca2+ released from the SR binds to troponin of thin filament
• Binding causes tropomyosin to be pulled away from actin's myosin binding site so that Myosin can then bind to actin forming key linkage

The Powerstroke

• Myosin has an ATP binding site and uses ATP to cock the myosin head for interaction: ATP becomes ADP + Pi
• If myosin-binding site available, myosin binds actin
• The interaction then leads to a powerstroke which causes release of original ADP + Pi
• New ATP binds ATPase site causing release of myosin from actin

Contraction Mechanics

• The filaments do not get smaller, but the length of the bands shrink as Thin filaments slide inward over the stationary thick filaments towards the center of the A band
• As the thin filaments move, they pull the Z lines closer together which shortens the sarcomere
• H zone and I bands get shorter, while A band stays the same length

Relaxation Mechanics

• AChE removes any ACh ensuring no EPP
• SR has Ca2+-ATPase pump (called SERCA) actively pumps Ca2+ from the cytosol into the SR
• With no Action Potential, there is no Ca2+ release and Ca2+ pumped out of cytosol so actin and myosin can not interact

ATP Importance

• There are limited stores of ATP in muscles, so muscles must use different pathways to supply additional ATP during contractions depending on need:
• Immediate Supplies via the phosphagen system
• Short-term Supplies via anaerobic cellular respiration
• Long-term supplies are provided via aerobic cellular respiration

Phosphagen System

• Immediate energy, requires no oxygen and is the first responder
• Immediate formation of ATP, gets burned early and quickly
• Small amounts of stored ATP which is hydrolyzed by ATPase to release energy and provide about 5-6 secs worth of energy
• Myokinase transfers Pi from ADP to another ADP to make ATP (about 2 secs energy)
• Creatine Phosphate serves as storage for Pi and Creatine Kinase transfers Pi between Creatine Phosphate and ADP to make ATP
• The reverse reaction stores energy and provides 10-15 secs of energy

Short and Long Term Energy

• Short term: Anaerobic cellular respiration
• Some glucose stored in the muscle as glycogen
• Pyruvate from Glycolysis converts to lactic acid instead of entering into TCA
• This is performed as a last resort to try and occur rapidly
• Long-term: Aerobic cellular respiration, requiring O2 that is relatively slow and dependent on nutrients being delivered to the muscle
• Has a high yield of ATP, and myoglobin increases rate of O₂ transfer from the blood to muscle