Histology of Skeletal Muscle
Skeletal muscle is a excitable, contractile tissue responsible for maintaining posture and moving the orbits, together with the appendicular and axial skeletons. It attaches to bones and the orbits through tendons. Excitable tissue responds to stimuli through electrical signals. Contractile tissue is able to generate tension of force. Skeletal muscle tissue is also extensible and elastic. Extensible tissue can be stretched and elastic tissue is able to return to its original shape following distortion.
Special terms are used to describe structures associated with skeletal muscle tissue. Muscle tissue terms often begin with myo-, mys-, or sarco-. The cytoplasm of a muscle cells is referred to as sarcoplasm. The plasma membrane is called the sarcolemma and the endoplasmic reticulum is called the sarcoplasmic reticulum. A muscle fiber may also be referred to as a myofiber.
Individually, skeletal muscles cells are referred to as muscle fibers. The length of a skeletal muscle fiber varies by location. In the anterior thigh, a muscle fiber may be a meter long. In contrast, muscle fibers making up the stapedius, a small muscle of the inner ear, are only a few millimeters in length. Myofibrils are rod shaped subunits of muscle cells. The actin and myosin filaments making up the myofibrils are organized into sarcomeres. Under a microscope, sarcomeres give skeletal muscle a striated appearance.
Skeletal muscle tissue develops through the fusion of individual myoblasts, or early muscle cells. This fusion results in a characteristic multinucleated structure. Because the cells are fused and multinucleated, they form a structural syncytium. Nuclei of skeletal muscle tissue are oval-shaped and located at the periphery of the cell. They are accompanied by satellite cells between the external lamina and sarcolemma. Satellite cells are precursors to skeletal muscle cells and are responsible for the ability of muscle tissue to regenerate. They have a small amount of cytoplasm and because of their locations can sometimes be mistaken for skeletal muscle cell nuclei.
Skeletal Muscle Fibers
Skeletal muscle tissue is made up of a collection of muscle fibers wrapped in connective tissue sheaths. There are three types of connective tissue sheaths named for their location. Endomysium surrounds individual muscle fibers. It is made up of a delicate layer of reticular fibers and permits only small-diameter nerve fibers and capillaries, thus acting as a site of metabolic exchange.
Perimysium is a slightly thicker layer of connective tissue consisting mainly of type I and III collagen and surrounds a group of fibers. This fiber group is referred to as a fascicle or bundle. Fascicles are the functional units of skeletal muscle tissue.
The perimysium contains slightly larger blood vessels and nerve fibers than those traveling through endomysium.
Epimysium surrounds the entire collection of fascicles making up an individual muscle. This dense connective tissue made up of mainly type I collagen contains the neurovascular supply to the muscle.
There are three types of skeletal muscle fibers: Type I, Type IIa, and Type IIb.
- Type I muscle fibers, also called slow oxidative fibers, are specialized for aerobic activity. They are small, contain a high amount of myoglobin, and appear red in fresh tissue. A muscle twitch is a single contraction of a muscle. Type I fibers make up slow-twitch, fatigue-resistant motor units. Muscles of the deep back responsible for maintaining posture are mostly made up of Type I slow oxidative fibers.
- Type IIa muscle fibers are also known as fast oxidative glycolytic fibers. These fibers appear slightly lighter than Type I in fresh tissues. They contain many mitochondria and have a higher myoglobin content than type IIb fibers. Unlike Type I fibers, Type IIa fibers have high amounts of glycogen. Because of this they are capable of anaerobic glycolysis and make up fast-twitch, fatigue resistant motor units. Type IIa fibers are more fatigue resistant than Type IIb fibers and are used in movements that require high sustained power. Many athletes have high amounts of these fibers, especially competitive swimmers.
- Type IIb muscle fibers are also referred to as fast glycolytic fibers. They are large fibers and appear light pink in fresh tissues. Type IIb fibers contain fewer mitochondria and a lower amount of myoglobin. Although they contain a low level of oxidative enzymes, they show high anaerobic enzyme activity and contain a high amount of glycogen. Type IIb fibers are more prone to fatigue than Type I and Type IIa fibers and make fast-twitch, fatigue prone motor units. Type IIb fibers have the fastest rate of ATPase activity and are found in muscles used for short, rapid bursts of contraction such as the gastrocnemius, a muscle in the leg that is used in jumping.
The sarcomere is the functional unit of a skeletal muscle cell. Each sarcomere is about 2.5 micrometers in length. It is made up of multiple myosin and actin filaments oriented in parallel. The actin and myosin filaments overlap in certain places creating several bands and zones. A Z disc forms the boundary of the sarcomere on either side. Thin actin filaments project in either direction off of a Z disc but do not cross the entire length of the sarcomere. They are almost 8 nm in diameter and have tightly bound regulatory proteins called troponin and tropomyosin.
The center of the sarcomere lacks actin filaments and is referred to as the H zone. An M line runs down the middle of the H zone perpendicular to the filaments. Thick myosin filaments are found between the actin filaments. Their diameter is approximately 15 nm with a globular head region consisting of heavy and light chain. This head has an ATPase activity and ability to bind and move along actin filament. They are not connected to the Z discs but do traverse the H zone.
The sarcomere is broken up into three bands. The A band is in the middle and corresponds to the myosin filaments together with the thin filaments overlapping on both ends. There are two I bands on either side of the A band and represent the area in which only actin filaments are present.
- Sarcolemma - cell plasma membrane of a muscle cell
- Sarcoplasmic reticulum - modified endoplasmic reticulum. The sarcoplasmic reticulum resembles a piece of lace that surrounds the myofibril. It is made up of a network of tubules with a reservoir at either end. This reservoir is referred to as the terminal cisterna.
- Terminal cisterna - enlarged regions on either end of the sarcoplasmic reticulum. The terminal cisternae sequester calcium to be used in the contraction cycle. There is a terminal cisterna on either side of a t-tubule. All together they are called a triad.
- T-tubules - also called transverse tubules. The t-tubules are pits along the surface of the muscle cells. Their walls are continuous with the sarcolemma, meaning the internal surface of the t-tubule is exposed to the extracellular matrix. The t-tubules are responsible for moving action potentials to the inner region of the muscle cell.
The thick and thin filaments in the myofibrils are supported by accessory proteins. These proteins maintain the speed and alignment of filaments during the contraction cycle. Some of them are described below.
- Titin is a large, elastic protein the anchors thick filaments to Z lines to prevent excessive stretching of the myofibril
- Tropomodulin acts like an actin cap. It attaches to the free end of an actin filament to maintain its length.
- α-Actinin is a short, rod-shaped protein that arranges thin filaments into parallel bundles and anchors them to the Z line
- Desmin is an intermediate filament that forms a lattice surrounding the sarcomere near the Z lines to attach them to each other and the plasma membrane.
- Nebulin is a thin, elongated protein running parallel to thin filaments. It assists α-Actinin in binding the thin filaments to the Z line and is thought to be important during the development of muscle tissue.
- Dystrophin is thought to link actin filaments to the external lamina of the muscle cell
- Myomesin anchors thick filaments to the M line.
A neuromuscular junction, abbreviated NMJ, is the location at which a motor nerve ending makes a synapse with a muscle cell. Motor neurons release acetylcholine into the synaptic cleft of the neuromuscular junction. The acetylcholine molecules traverse the synaptic cleft and bind to receptors on the muscle fiber membrane. This results in depolarization and subsequent contraction of the muscle cell.
The mechanism for muscle contraction is referred to as the sliding filament theory. In this process, actin and myosin filaments slide past each other shortening the sarcomere. The sliding filament mechanism requires the hydrolysis of adenosine triphosphate (ATP) molecules and the binding and release of myosin heads on actin filaments.
- Following excitation by a motor nerve ending, ATP binds to myosin, decreasing the affinity of actin to myosin. Myosin releases actin.
- Myosin hydrolyses ATP to adenosine diphosphate (ADP) and a phosphate molecule. This provides energy needed for the myosin head to rotate to a 90° angle and reattach to a new actin.
- Power stroke - When the muscle is not contracting, the myosin binding site is partially blocked by a troponin molecule. During contraction calcium binds to troponin, decreasing its affinity to the myosin binding site and uncovering it so that myosin binds more tightly and releases a phosphate. The release of phosphate causes the myosin head to swing toward the M line and the attached actin filament slides with it.
- At the end of the power stroke, myosin releases the ADP molecule. The head returns to its original position and is ready to begin the cycle again.
Control of Skeletal Muscle Contraction
Two main proprioceptors influence the strength and duration of muscle contraction: Golgi tendon organs and muscle spindle fibers. Golgi tendon organs relay information about the force of contraction. Muscle spindles detect changes in muscle length.
Golgi Tendon Organs
Golgi tendon organs are receptors found at the junction between myofibrils and tendons. The receptor endings of a Golgi tendon organ are intertwined with the collagenous fibers of the tendon. When the muscle in contracted, the tendon is stretched and the receptors are compressed in a web of connective tissue. The pressure initiates an action potential in the nerve ending and sends a signal through the central nervous system. The role of the Golgi tendon organ is to prevent muscles from over-contracting.
Muscle Spindle Fibers
Muscle spindles detect change in muscle length, position, and velocity. Muscle spindle fibers are long, thin encapsulated fibers aligned in parallel to myofibrils. They are also called intrafusal muscle fibers, while extrafusal fibers are are present outside the spindle capsule. The ends of the intrafusal muscle fibers are attached to myofibrils so that when the muscle is stretched, the muscle spindle fibers stretch as well. Stretching the spindle causes it to depolarize and relay that information through the spinal cord.
Muscular dystrophy is an umbrella term for a series of disorders involving mutations in DNA coding for dystrophin proteins. The damaged dystrophin results in the breakdown and weakening of muscle tissue. Some examples include Duchenne and Becker muscular dystrophy, and facioscapulohumeral muscular dystrophy. Although there is a genetic link, the disorders have a wide range of phenotypic presentations and require many tests to determine a correct diagnosis.
Actin aggregate myopathy
Actin aggregate myopathy, also called actin accumulation myopathy is a disorder in which actin filaments accumulate in skeletal muscle fibers. This causes severe muscle weakness and decreased muscle tone. Individuals with actin aggregate myopathy often do not survive past infancy because the diaphragm, the main muscle used in respiration, can not function. Individuals who survive tend to have poor posture and fine motor skills and difficulty walking.
Myotubular (Centronuclear) Myopathies
Myotubular myopathy, a genetic disorder caused by a mutation in the dynamin protein, is characterized by large, central nuclei. The nuclei are surrounded by an area densely packed with mitochondria but lacking myofibrils. The resulting muscle fibers tend to be small and round in shape.Patients with myotubular myopathy often present with paralysis of extraocular muscles.