Muscle tissue
Abstract
Muscle tissue is largely composed of actin (thin) and myosin (thick) filaments, which work in a coordinated effort to generate force and, in turn, muscle contraction. Depending on the intracellular arrangement of these myofilaments, muscle tissue is classified as either striated (skeletal and cardiac) or nonstriated (smooth) muscle. The myofilaments of striated muscle are arranged into sarcomeres; smooth muscle lacks this arrangement. Although the different types of muscle follow very similar principles on a molecular level (sliding filament mechanism), their functions vary greatly. Skeletal muscle is attached to the skeleton and provides voluntary movement. Smooth muscle possesses greater elasticity and is primarily found in the walls of hollow internal organs, where it contracts and relaxes involuntarily to fulfill a wide range of functions. In the intestine, for example, smooth muscle is responsible for transporting the bolus, whereas in the blood vessels it is primarily responsible for ensuring vascular resistance in circulation.
Muscle cells (myocytes)
Overview
- Function: produce a contraction or generate tension
- Origin: mesoderm
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Histological classification
- Striated muscle fibers
- Smooth muscle fibers:
Muscle cell structures
Muscle cell structure | Characteristics |
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Sarcolemma |
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Sarcoplasm |
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Myofilaments |
Types of skeletal muscle fibers
Type 1 fibers (e.g. postural muscles) | Type 2 fibers (extraocular muscles) | |
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Appearance |
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Energy production |
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Myosin ATPase activity |
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Contraction velocity |
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Activity period |
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Structural differences between muscle cell types
Skeletal muscle | Cardiac muscle | Smooth muscle | |
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Cell morphology |
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Invaginations of the sarcolemma |
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Arrangement of myofilaments
Myofilaments are protein fibers consisting of thick (myosin) and thin (actin) filaments.
Types
Actin myofilaments
- Function: Actin thin filaments serve as an anchored tether upon which myosin slides to allow contraction
- Stabilization: Regulatory proteins such as nebulin and tropomyosin accompany actin and prevent polymerization.
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Contain regulatory proteins : Prevent permanent interaction between myosin and actin.
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Proteins that block myosin binding sites:
- In both striated and smooth muscle: tropomyosin
- Only in smooth muscle:
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Proteins that interact with calcium:
- In striated muscle: troponin
- In smooth muscle: calmodulin
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Proteins that block myosin binding sites:
Myosin filaments
- Function: Thick filament that slides along actin filaments, which is driven by ATP hydrolysis
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Structure
- Myosin filaments contain ∼ 300 myosin molecules.
- The myosin molecule is composed of a tail and a head, which are formed from several heavy and light chains depending on the myosin type.
Both striated and smooth muscle cells mediate contractions via actin and myosin!
The structure of troponin complex proteins differs slightly in cardiac and skeletal muscles. In myocardial infarction, cardiac myocytes are damaged as a result of absolute oxygen deficiency and release their intracellular content into the bloodstream. An increase in cardiac troponin levels in blood indicates cardiac muscle tissue damage.
Two types of arrangement of myofilaments
- Smooth muscle: disorganized
- Striated muscle: sarcomere
Sarcomeres of striated muscle
- Definition: The smallest functional unit of a striated muscle fiber, which is the area between two Z lines.
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Components on electron microscopy
- Lines
- Z lines: separate one sarcomere from the other and act as an anchoring point for actin filaments (via anchoring proteins such as α-actinin) (very dark on electron microscopy)
- M lines: center of the H zone, to which myosin filaments are attached on opposite sides
- Bands
- I bands: zone containing only (thin) actin filaments
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A bands
- The length of a myosin filament, which may contain overlapping actin filaments (keeps its length during contraction!)
- Composed of three segments
- Lines
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Anchorage by:
- Intermediate filaments (especially desmin): crosslink Z lines and anchor in the sarcolemma
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Dystrophin-glycoprotein complex: links (noncontractile) actin of the cytoskeleton with the sarcolemma and extracellular matrix:
- Duchenne muscular dystrophy and Becker muscular dystrophy involve genetic defects of the dystrophin gene.
- Collagen fibrils: anchor muscle cell to the endomysium
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Titin: a protein between the M line and Z line that acts as a molecular spring, returning the sarcomere to its initial state after contraction.
- Limits the passive elasticity of a muscle and protects against damage.
During muscle contraction:
- Thick (myosin) and thin (actin) filaments DO NOT shorten in length.
- A bands remain the same length
- Z lines come closer together
- I bands and H zone decrease in size.
Myofilament contraction
At resting position, actin and myosin are unable to interact because they are inhibited by regulatory proteins (e.g., tropomyosin), which require an initiating stimulus to undo.
Initiation of muscle contraction
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Initiating stimuli
- Electromechanical coupling: Translation of the electrical signal from the sarcolemma into a muscle contraction.
- Pharmacomechanical coupling: Triggering of a muscle contraction via pharmaceutical agonists such as acetylcholine, noradrenaline, or histamine.
- Steps: Stimulus (e.g., action potential) from efferent neuron opens presynaptic voltage-gated calcium channels → ACh released into the synaptic gap → ACh binds to postsynaptic ACH receptors → causes muscle cell depolarization that diffuses across the sarcolemma and into T-tubules or caveolae → Depolarization opens voltage-sensitive dihydropyridine receptors (DHPR) and the mechanically coupled ryanodine receptors (RR) in the SR → SR releases calcium → ↑ intracellular calcium
Skeletal muscle contraction results from an increase in intracellular calcium from stores in the sarcoplasmic reticulum. This explains the ability of skeletal muscle to contract despite treatment with calcium channel blockers, which can block an influx of extracellular calcium through DHPRs but cannot affect DHPR voltage-sensing capabilities and the resulting intracellular calcium release.
Steps of the contraction cycle (sliding filament theory)
- Orientation of the myosin head: hydrolysis of ATP to ADP and Pi (both remain on the myosin head) → myosin head alters its confirmation (“cocked state”) → it is ready to bind actin once
- Crossbridge formation: intracellular calcium binds troponin and causes a conformational change → moves tropomyosin out of the myosin binding site on actin → myosin head binds actin at a 90° angle, forming a crossbridge
- Powerstroke of the myosin head: Myosin head releases ADP and Pi → myosin head turns by 45°, pulling myosin along actin → muscle shortens
- Loosening of the crossbridge: ATP binds myosin head → detaches from the actin filament → myosin head returns to its starting position
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Replication of the cycle: If calcium concentration in the muscle cell remains elevated → a new cycle begins with reorientation of the myosin head.
- Depending on ATPase activity (ATP cleavage rate per unit of time) of the heavy myosin chain, there may be ∼ 10–100 crossbridge cycles per second.
- The more crossbridge cycles per unit of time, the faster and stronger the contraction.
When a person dies and breathing and circulation stop, muscle cells lack oxygen and cannot use aerobic respiration to efficiently produce ATP anymore. Without ATP, the crossbridges between myosin and actin filaments cannot be resolved and muscles become tense, which is referred to as rigor mortis.References:[1][2][3][4]
Energy provision for muscle contraction
ATP is required by muscle cells as an energy source for:
- Maintaining structure and ion gradients
- Interaction between the myosin head and actin that leads to muscle contraction
Sources of ATP synthesis
- Storage of ATP is very limited and requires reproduction.
- The source of ATP reproduction depends on the energy demands of the activity.
- ATP ultimately derives from nutritional sources
Source | Characteristics | Calories (kcal/g) |
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Protein |
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Glucose |
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Fat |
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Aerobic sources
- Main sources when energy demand does not override the availability of oxygen for ATP creation (e.g., walking)
- Formed from oxidative formation via the citric acid cycle and respiratory chain from metabolic products of either:
- Glucose (from glycolysis) or
- Fatty acids (from β oxidation)
Anaerobic sources
Anaerobic glycolysis
- Main source when energy demand overrides the availability of oxygen for ATP creation (e.g., sustained sprint)
- Glucose → pyruvate → lactic acid + 2 ATP
- Does not require oxygen → can continue even when energy demand exceeds oxygen supply
- See anaerobic glycolysis for more information.
Creatine phosphate
- Together with readily available ATP, forms the phosphagen system
- As with stored ATP, utilized primarily during very short bursts of rapid movement, which requires a very high availability of energy immediately (e.g., start of a sprint, powerlifting)
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Creatine kinase transfers the phosphate from creatine phosphate to ADP → quickly creates ATP and creatine
- One form of creatine kinase also creates creatine phosphate from ATP and creatine
- Storage of creatine phosphate is very limited
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Creatine
- Synthesis: in two steps
- Degradation
- Creatine phosphate is converted to creatinine through removal of phosphate residues and cyclization.
- Excretion in urine: Creatinine is entirely removed by glomerular filtration.
In addition to the ATP supply, creatine phosphate is an important short-term energy store in the muscle cell!
The creatinine concentration in urine is proportional to the glomerular filtration rate.
Adenylate kinase (myokinase)
- Another anaerobic form of immediate ATP reproduction
- An enzyme of the mitochondrial intramembrane space transfers a phosphate residue from one ADP to the other, which makes ATP available (ADP + ADP ↔ ATP + AMP)
Glucose-alanine cycle (Cahill cycle)
- Definition: metabolic cycle in which alanine (from protein degradation) is transported from skeletal muscle to the liver and receives glucose in exchange for energy production
- Key enzyme: alanine aminotransferase (ALT)
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Process
- Alanine is released during muscle protein degradation.
- Alanine is transported by blood to the liver, where it is transaminated to pyruvate by the enzyme alanine aminotransferase (ALT).
- Gluconeogenesis is responsible for the conversion of pyruvate to glucose, which is released in blood and transported to the muscle.
- Glucose can be degraded in the muscle, serving as a source of energy.
- A byproduct of energy production from alanine is production of urea (consumes a lot of energy).
- Pathway usually only used in states of muscle breakdown (catabolism)
The glucose-alanine cycle does not result in the organism gaining energy in the thermodynamic sense, but serves to provide muscles with glucose!
Lactic acid cycle (Cori cycle)
- Definition: metabolic cycle in which lactate (from anaerobic glycolysis in muscle) is transported to the liver, where it is converted into glucose, which is transported back to the muscles for energy production
- Key enzyme: lactate dehydrogenase (LDH)
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Process
- In the absence of oxygen in active skeletal muscle, LDH catalyzes the reduction of pyruvate to lactate (anaerobic glycolysis).
- Lactate is transported within the blood to the liver, where it is converted into pyruvate by the enzyme LDH.
- Pyruvate serves as the source of gluconeogenesis: it is converted into glucose and transported to the muscle.
- Glucose can be degraded in the muscle, serving as a source of energy.
Comparison of muscle tissue types
Comparison of contractile filaments
Skeletal muscle/cardiac muscle | Smooth muscle | |
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Organization/orientation | Sarcomere | Disorganized |
Interaction with calcium | Troponin | Calmodulin |
Myosin binding site blockage | Tropomyosin | Tropomyosin with caldesmon and calponin |
Anchorage | Z lines (skeletal muscle)/intercalated discs (cardiac muscle) | Dense bodies |
Phosphorylation of the light myosin chain required | No | Yes |
Comparison of stimulation and contraction
Skeletal muscle | Cardiac muscle | ||
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Initiating structure or stimulus |
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Special features of electromechanical coupling |
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Function as a unit |
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Clinical significance
- Duchenne muscular dystrophy
- Becker muscular dystrophy
- Myocardial infarction
- Rigor mortis
- McArdle disease
- Trichinellosis
- Rhabdomyoma (benign)
- Rhabdomyosarcoma (malignant)
- Cancer cachexia
- Polymyositis
- Dystonia
- Myoclonus
- Malignant hyperthermia
- Botox
- Myasthenia gravis
- Skeletal muscle relaxants
- Muscle power grading
- Electromyography