Muscle biology - Georgine Faulkner and muscle plasticity definitions
First I would like to point out that cardiacand skeletal muscle are known as striated muscle.
Smooth muscle is primarily under the control of autonomic nervous system, whereas skeletal muscle is under the control of the somatic nervous system. The single-unit smooth muscle has pacemaker regions where contractions are spontaneously and rhythmically generated. The fibres contract in unison, that is the single unit of smooth muscle is syncytial. The fibres of multi-unit smooth muscle are innervated by sympathetic and parasympathetic nerve fibres and respond independently from each other upon nerve stimulation.
Atrophy is a decrease in cell size and/or number in a previously normal tissue or organ. Decrease in cell number is mediated by apoptosis; decrease in cell size by a reduction in cell growth. Atrophy can be physiological or pathological.
Skeletal muscle atrophy
Skeletal muscle atrophy is a change that occurs in muscles of as a result of disuse (e.g., immobilization, denervation, muscle unloading), aging, starvation, and a number of disease states (i.e., cachexia). Regardless of the inciting event, skeletal muscle atrophy is characterized by a decrease in protein content, fibre diameter, force production, and fatigue resistance. The different types of conditions producing atrophy imply different types of molecular triggers and signaling pathways for muscle wasting.
Decrease in cell mass due to shrinking of the individual cell caused by protein degradation. (Elizabeth) Cardiac Atrophy: A decrease in size of the heart. It can be brought on by prolonged immobilization or "wasting" that can occur with debilitating, chronic illnesses (e.g., anorexia). Left ventricle atrophy affects the lower left chamber of the heart
smooth muscle atrophy
Skeletal and cardiac muscleadapt to hormonal and neuronal stimuli and can rapidly hypertrophy and atrophy, however the extent to which these processes occur in smooth muscle is less clear. Atrophy in striated muscle results from enhanced protein breakdown, and is associated with a common transcriptional profile and activation of the ubiquitin proteasome pathway including induction of the muscle-specific ubiquitin protein ligases atrogin-1 and MuRF-1. Atrogin-1 is also expressed in smooth muscle, and that both atrogin-1 and MuRF-1 are upregulated in the uterus following delivery, as rapid involution occurs.
Some examples of physiological atrophy ·In the embryo & fetus, the notochord and branchial clefts undergo atrophy. ·In the neonate, the umbilical vessels and ductus arteriosus undergo atrophy. ·In early adulthood, the thymus undergoes atrophy.
Some examples of pathological atrophy · Loss of function causes muscle atrophy and osteoporosis in immobilisation or weightlessness. · Loss of innervation causes muscle atrophy in nerve transection or poliomyelitis. · Loss of blood supply causes skin atrophy or bedsores in peripheral vascular disease or excess pressure. · Severe malnutrition causes atrophy in many tissues. · Loss of hormonal stimulation causes atrophy of adrenal cortex, thyroid, and gonads in hypopituitarism. · Excess hormones can cause atrophy: excess corticosteroids cause skin atrophy.
Both hyperplasia and hypertrophy can be physiological or pathological. Hyperplasiais an increase in cell number by cell division, often leading to an increase in the size of an organ. Skeletal muscle hyperplasia:Hypertrophy refers to an increase in the size of the cell while hyperplasia refers to an increase in the number of cells or fibres. A single muscle cell is usually called a fibre. Cardiac hyperplasia , increase in number of cells, is a characteristic of foetal life except for the first few weeks of neonatal life in some mammals, postpartum growth is hypertrophic.
Some examples of physiological hyperplasia: · The breast undergoes hyperplasia during puberty, pregnancy, and lactation, stimulated by hormones such as oestrogens, progesterone and prolactin. · Red cell precursors in the bone marrow undergo hyperplasia at high altitude, stimulated by erythropoietin, which has been evoked by hypoxia. · The thyroid undergoes hyperplasia in puberty and pregnancy, stimulated by increased metabolic demand.
Some examples of pathological hyperplasia: . The prostate gland undergoes hyperplasia, stimulated by oestrogen. · The adrenal cortex undergoes hyperplasia (Cushing’s syndrome) stimulated by ACTH produced by pituitary, lung or other tumours. · The thyroid gland undergoes hyperplasia in Graves’ disease, stimulated by Thyroid-stimulating autoantibody. · The parathyroid gland undergoes hyperplasia stimulated by hypercalcaemia. · The endometrium undergoes hyperplasia stimulated by oestrogen. · Myointimal cells undergo hyperplasia in atheromatous plaques stimulated by Platelet Derived Growth Factor. · Keratinocytes in skin undergo hyperplasia in psoriasis, stimulated by cytokines released in an immune response.
Hypertrophy is an increase in cell size without cell division, usually leading to an increase in the size of an organ. Skeletal muscle hypertrophy:Hypertrophy, an increase in mass of a muscle and cross-sectional area. It can be induced by a number of stimuli such as exercise.The increase in dimension is due to an increase in the size (not length) of individual muscle fibres. Cardiac hypertrophy: Cardiac enlargement refers to an increase in the size of the heart. There are two types of cardiac enlargement: hypertrophy and dilation. Hypertrophy involves an increase in the thickness of the heart muscle. Dilation involves an increase in the size of the inside cavity of a chamber of the heart. Hypertrophy usually occurs in only one chamber while dilation may occur in one, two, three, or all of the chambers, based on its cause. In most cases, cardiac enlargement is abnormal and accompanied by additional cardiovascular problems. The one exception is regular aerobic exercise, which produces a beneficial enlargement involving both hypertrophy and dilation of the heart. Both cardiac and skeletal muscle adapt to regular, increasing work loads that exceed the preexisting capacity of the muscle fibre. As a result of hypertrophy in cardiac muscle, the heart becomes more effective at squeezing blood out of its chambers, whereas skeletal muscle becomes more efficient at transmitting forces through tendonous attachments to bones smooth muscle hypertrophy: smooth muscle cells in the uterine wall during pregnancy increase in not only size (hypertrophy ) but also in number (hyperplasia) because these cells retain the capacity for cell division.
Some examples of physiological hypertrophy · Skeletal muscle undergoes hypertrophy stimulated by increased muscle activity on exercise. · Cardiac muscle undergoes hypertrophy stimulated by sustained outflow increase in athletes. · Myometrium undergoes hypertrophy in pregnancy stimulated by oestrogens.
Some examples of pathological hypertrophy · Cardiac muscle of the left ventricle undergoes hypertrophy because of increased outflow pressure eg systemic hypertension, aortic valve disease · Cardiac muscle of the right ventricle undergoes hypertrophy because of increased outflow pressure eg pulmonary hypertension, pulmonary valve disease. · Arterial smooth muscle undergoes hypertrophy in hypertension. · In old age the uterus, testes, brain and bone all atrophy.
Abnormal differentiation When mature tissues grow and differentiate abnormally, they can undergo metaplasia, dysplasia or both.
Metaplasia · Is defined as the transformation of one fully differentiated cell type into another. · Is an adaptive response to environmental stress, usually chronic irritation or inflammation; metaplastic tissues are better able to withstand the adverse environmental changes than are normal tissues · Is caused by activation and/or repression of groups of genes involved in the maintenance of cellular differentiation · There is no intrinsic gene defect (as there is in neoplasia), therefore metaplasia is reversible. · But, metaplastic tissues are more genetically unstable than their normal counterparts, so they may undergo further transformation to dysplasia and neoplasia · Can affect epithelial or connective tissue cells
Plasticity is adaptability to change or flexibility, in responseto functional demands, with consequent modifications to structural and/or functional phenotypes. In biology, phenotypic plasticity is an ability of a genotype to express different phenotypes, adaptive or environmentally constrained by experience.
Skeletal muscle plasticity Regarding adaptations to change function, gene expression and structural phenotype in relation to demand or environmental pressure, satellite cells are the `agent' of rapid, prolonged and persistent change during muscle development, growth, responses to disease or injury, and regeneration. In adult skeletal muscle, the self-renewing capacity of satellite cells contributes to muscle growth, adaptation and regeneration. Muscle remodeling, such as demonstrated by changes in myofibre cross-sectional area and length, nerve and tendon junctions, and fibre-type distribution,occur in the absence of injury and provide broad functionaland structural diversity among skeletal muscles.
Cardiac muscle cell plasticity Heart muscle can grow during most of the lifespan and it has significant capability of adaptation and plasticity. An increase in the work load (preload and/or afterload) and activity (heart rate) control the growth and properties of the muscle cells. The triggers for the adaptation are believed to be changes in the activities of ion channels acting in concert with complex Ca2+ signalling mechanisms of the cells. These mechanisms form the basis of the extreme plasticity of cardiac muscle. The development of pathological hypertrophy is associated with a return to the foetal pattern of cardiac gene expression and changes in myocardial contractility, indicating that even the mechanisms involved in embryonic development of the heart can be re-established.
Smooth muscle plasticity Smooth muscle cells possess remarkable phenotypic plasticity that allows rapid adaptation to fluctuating environmental cues. For example, vascular smooth muscle cells undergo profound changes in their phenotype during neointimal formation in response to vessel injury or within atherosclerotic plaques. Mature smooth muscle cells are unique among muscle cell lineages, because they can change phenotype in response to a variety of stimuli. This ability to conform to changing stimuli or microenvironments is referred to as plasticity. Many patho-physiological conditions include or result from phenotypic changes in smooth muscle tissues, but the cause and consequences of remodeling and hypertrophy are not well understood.
myofibril Long, highly organized bundle of actin, myosin, and other proteins in the cytoplasm of muscle cells that contracts by a sliding filament mechanism.
Muscle Fibre Types Skeletal muscle fibers are not all the same. All skeletal muscle fibres are not alike in structure or function. For example, skeletal muscle fibres vary in colour depending on their content of myoglobin (myoglobin stores oxygen until needed by mitochondria). Red Fibres: Those containing high levels of myoglobin and oxygen storing proteins had a red appearance. Red muscle fibers tend to have more mitochondria and blood vessels than the white ones. White Fibers: Those with a low content of myoglobin have a white appearance.
Skeletal muscle fibres are also classified, depending on their twitch capabilities, into fast and slow twitch. Skeletal muscle fibres contract with different velocities, depending on their ability to split Adenosine Triphosphate (ATP). Faster contracting fibres have greater ability to split ATP. In addition, skeletal muscle fibres vary with respect to the metabolic processes they use to generate ATP. They also differ in terms of the onset of fatigue. Based on various structural and functional characteristics, skeletal muscle fibres are classified into three types: Type I fibres, Type II B fibres and type II A fibres. Most skeletal muscles of the body are a mixture of all three types of skeletal muscle fibres, but their proportion varies depending on the usual action of the muscle. For example, postural muscles of the neck, back, and leg have a higher proportion of type I fibres. Muscles of the shoulders and arms are not constantly active but are used intermittently, usually for short periods, to produce large amounts of tension such as in lifting and throwing. These muscles have a higher proportion of type I and type II B fibres. The average person has approximately 60% fast muscle fibre and 40% slow-twitch fibre (type I).
Type I Fibres These fibres, also called slow twitch or slow oxidative fibres, contain large amounts of myoglobin, many mitochondria and many blood capillaries. Type I fibres are red, split ATP at a slow rate, have a slow contraction velocity, very resistant to fatigue and have a high capacity to generate ATP by oxidative metabolic processes. Such fibres are found in large numbers in the postural muscles of the neck.
Red fibres. Slow oxidative (also called slow twitch or fatigue resistant fibers). Contain: Large amounts of myoglobin. Many mitochondria. Many blood capillaries. Generate ATP by the aerobic system, hence the term oxidative fibers. Split ATP at a slow rate. Slow contraction velocity. Resistant to fatigue. Found in large numbers in postural muscles. Needed for aerobic activities like long distance running.
Type II A Fibres
These fibres, also called fast twitch or fast oxidative fibres, contain very large amounts of myoglobin, very many mitochondria and very many blood capillaries. Type II A fibres are red, have a very high capacity for generating ATP by oxidative metabolic processes, split ATP at a very rapid rate, have a fast contraction velocity and are resistant to fatigue. Such fibres are infrequently found in humans.
Red fibres Fast oxidative (also called fast twitch A or fatigue resistant fibres). Contain: Large amounts of myoglobin. Many mitochondria. Many blood capillaries. High capacity for generating ATP by oxidation. Split ATP at a very rapid rate and, hence, high contraction velocity. Resistant to fatigue but not as much as slow oxidative fibers. Needed for sports such as middle distance running and swimming.
Type II B Fibres These fibres, also called fast twitch or fast glycolytic fibres, contain a low content of myoglobin, relatively few mitochondria, relatively few blood capillaries and large amounts glycogen. Type II B fibres are white, geared to generate ATP by anaerobic metabolic processes, not able to supply skeletal muscle fibres continuously with sufficient ATP, fatigue easily, split ATP at a fast rate and have a fast contraction velocity. Such fibres are found in large numbers in the muscles of the arms. The fast muscle (type IIa) moves 5 times faster than the slow muscle, and the super-fast (type IIb) moves 10 times faster than the slow muscle fibre.
White. Fast glycolytic (also called fast twitch B or fatiguable fibres). Contain: Low myoglobin content. Few mitochondria. Few blood capillaries. Large amount of glycogen. Split ATP very quickly. Fatigue easily. Needed for sports like sprinting.
Fibre type modification
Various types of exercises can bring about changes in the fibres in a skeletal muscle.Endurance type exercises, such as running or swimming, cause a gradual transformation of type II B fibres into type II A fibres. The transformed muscle fibres show a slight increase in diameter, mitochondria, blood capillaries, and strength. Endurance exercises result in cardiovascular and respiratory changes that cause skeletal muscles to receive better supplies of oxygen and carbohydrates but do not contribute to muscle mass. On the other hand, exercises that require great strength for short periods, such as weight lifting, produce an increase in the size and strength of type II B fibres. The increase in size is due to increased synthesis of thin and thick myofilaments. The overall result is that the person develops large muscles. Fast-twitch muscle fibre can be developed by conducting plyometric or complex training (combination of plyometrics and weights) to build the fast muscle (IIa) and performing sprinting types of training to build the super-fast (IIb) to the point where you can release exercise-induced growth hormone.
Response to muscle activity
A single muscle fibre may contain 15 billion thick filaments. When that muscle fibre is actively contracting, each thick filament breaks down roughly 2,500 ATP molecules per second. Because even a small skeletal muscle contains thousands of muscle fibres, the ATP demands of a contracting skeletal muscle are enormous. In practical terms, the demand for ATP in a contracting muscle fibre is so high that it would be impossible to have all the necessary energy available as ATP before the contraction begins. Instead, a resting muscle fibre contains only enough ATP and other high-energy compounds to sustain a contraction until additional ATP can be generated. Throughout the rest of the contraction, the muscle fibre will generate ATP at roughly the same rate as it is used. The primary function of ATP is the transfer of energy from one location to another rather than the long-term storage of energy. At rest, a skeletal muscle fibre produces more ATP than it needs. Under these conditions, ATP transfers energy to creatine. The energy transfer creates another high-energy compound, creatine phosphate (CP), or phosphorylcreatine:
ATP + creatineADP + creatine phosphate
During a contraction, each myosin cross-bridge breaks down ATP, producing ADP and a phosphate group. The energy stored in creatine phosphate is then used to "recharge" ADP, converting it back to ATP through the reverse reaction:
ADP + creatine phosphateATP + creatine
The enzyme that facilitates this reaction is creatine phosphokinase (CPK or CK). A resting skeletal muscle fibre contains about six times as much creatine phosphate as ATP. But when a muscle fibre is undergoing a sustained contraction, these energy reserves are exhausted in only about 15 seconds. The muscle fibre must then rely on other mechanisms to convert ADP to ATP. Aerobic metabolism normally provides 95 percent of the ATP demands of a resting cell. In this process, mitochondria absorb oxygen, ADP, phosphate ions, and organic substrates from the surrounding cytoplasm. The substrates then enter the TCA (tricarboxylic acid) cycle (also known as the citric acid cycle or the Krebs cycle), an enzymatic pathway that breaks down organic molecules. The carbon atoms are released as carbon dioxide. The hydrogen atoms are shuttled to respiratory enzymes in the inner mitochondrial membrane, where their electrons are removed. After a series of intermediate steps, the protons and electrons are combined with oxygen to form water. Along the way, large amounts of energy are released and used to make ATP. The entire process is very efficient; for each organic molecule "fed" to the TCA cycle, the cell will gain 17 ATP molecules.
Resting skeletal muscle fibers rely almost exclusively on the aerobic metabolism of fatty acids to generate ATP. When the muscle starts contracting, the mitochondria begin breaking down molecules of pyruvic acid instead of fatty acids. The pyruvic acid is provided by the enzymatic pathway of glycolysis.
Glycolysis is the breakdown of glucose to pyruvic acid in the cytoplasm of a cell. It is called an anaerobic process, because it does not require oxygen. Glycolysis provides a net gain of 2 ATP and generates 2 pyruvic acid molecules from each glucose molecule. The ATP produced by glycolysis is thus only a small fraction of that produced by aerobic metabolism, in which the breakdown of the 2 pyruvic acid molecules in mitochondria would generate 34 ATP. Yet, because it can proceed in the absence of oxygen, glycolysis can be important when the availability of oxygen limits the rate of mitochondrial ATP production.
In most skeletal muscles, glycolysis is the primary source of ATP during peak periods of activity. The glucose broken down under these conditions is obtained primarily from the reserves of glycogen in the sarcoplasm. Glycogen is a polysaccharide chain of glucose molecules. Typical skeletal muscle fibres contain large glycogen reserves, which may account for 1.5 percent of the total muscle weight. When the muscle fibre begins to run short of ATP and CP, enzymes split the glycogen molecules apart, releasing glucose, which can be used to generate more ATP. As the level of muscular activity increases and these reserves are mobilized, the pattern of energy production and use changes.
Energy Use and the Level of Muscle Activity
In a resting skeletal muscle the demand for ATP is low. More than enough oxygen is available for the mitochondria to meet that demand, and they produce a surplus of ATP. The extra ATP is used to build up reserves of CP and glycogen. Resting muscle fibres absorb fatty acids and glucose that are delivered by the bloodstream. The fatty acids are broken down in the mitochondria, and the ATP generated is used to convert creatine to creatine phosphate and glucose to glycogen.
At moderate levels of activity, the demand for ATP increases. This demand is met by the mitochondria. As the rate of mitochondrial ATP production rises, so does the rate of oxygen consumption. Oxygen availability is not a limiting factor, because oxygen can diffuse into the muscle fiber fast enough to meet mitochondrial needs. But all the ATP produced is needed by the muscle fiber, and no surplus is available. The skeletal muscle now relies primarily on the aerobic metabolism of pyruvic acid to generate ATP. The pyruvic acid is provided by glycolysis, which breaks down glucose molecules obtained from glycogen in the muscle fiber. If glycogen reserves are low, the muscle fiber can also break down other substrates, such as lipids or amino acids. As long as the demand for ATP can be met by mitochondrial activity, the ATP provided by glycolysis makes a relatively minor contribution to the total energy budget of the muscle fibre.
At peak levels of activity, the ATP demands are enormous and mitochondrial ATP production rises to a maximum. This maximum rate is determined by the availability of oxygen, and oxygen cannot diffuse into the muscle fiber fast enough to enable the mitochondria to produce the required ATP. At peak levels of exertion, mitochondrial activity can provide only about one-third of the ATP needed. The remainder is produced through glycolysis.
When glycolysis produces pyruvic acid faster than it can be utilized by the mitochondria, pyruvic acid levels rise in the sarcoplasm. Under these conditions, pyruvic acid is converted to lactic acid.
The anaerobic process of glycolysis enables the cell to generate additional ATP when the mitochondria are unable to meet the current energy demands. However, anaerobic energy production has its drawbacks:
A skeletal muscle fibre is said to be fatigued when it can no longer contract despite continued neural stimulation. The cause of muscle fatigue varies with the level of muscle activity. After short peak levels of activity, such as running a 100-meter dash, fatigue may result from the exhaustion of ATP and CP reserves or from the drop in pH that accompanies the buildup of lactic acid. After prolonged exertion, such as running a marathon, fatigue may involve physical damage to the sarcoplasmic reticulum that interferes with the regulation of intracellular Ca2+ concentrations. Muscle fatigue is cumulative--the effects become more pronounced as more muscle fibers are affected. The result is a gradual reduction in the capabilities of the entire skeletal muscle.
If the muscle fibre is contracting at moderate levels and ATP demands can be met through aerobic metabolism, fatigue will not occur until glycogen, lipid, and amino acid reserves are depleted. This type of fatigue affects the muscles of long-distance athletes, such as marathon runners, after hours of exertion.
When a muscle produces a sudden, intense burst of activity at peak levels, most of the ATP is provided by glycolysis. After just seconds to minutes, the rising lactic acid levels lower the tissue pH, and the muscle can no longer function normally. Athletes who run sprints, such as the 100-meter dash, get this type of muscle fatigue.