Muscular Physiology PDF

Chapter 2: Muscular Physiology General characteristics 1. Types of muscles There are 03 types of muscles: skeletal, smooth and cardiac. 2. Functions of muscles Production of movements Maintaining posture Stabilization of joints Heat release I. Skeletal striated muscl...

Chapter 2: Muscular Physiology General characteristics 1. Types of muscles There are 03 types of muscles: skeletal, smooth and cardiac. 2. Functions of muscles Production of movements Maintaining posture Stabilization of joints Heat release I. Skeletal striated muscle (SSM) A. Experimental study of contraction 1. Mechanical phenomena (Figure 1) 2. Electrical phenomena (Figure 1) Figure1: Succession of events leading to muscle contraction 1  3. Fundamental properties The fundamental properties of skeletal muscle are: Excitability:ability to perceive and respond to a stimulus.The stimulus can be a neurotransmitter released by a nerve cell, the response is the production along the sarcolemma of an electrical signal which is the origin of the muscular contraction. Contractility:ability to contract forcefully in the presence of appropriate stimulation. Extensibility:stretching ability;When contracted, muscle fibers shorten, but when relaxed, they can be stretched beyond their resting length. Elasticity:ability of muscle fibers to return to their resting length when relaxed. B. Anatomical support of contraction Muscle fiber: a specialized cell adapted to the function of contraction. Muscle fibers are specialized in contraction: Their elongated shape is adapted to a possible shortening They contain mitochondria, necessary for the production of ATP (energy enabling contraction) They contain myofibrils in their cytoplasm which allow them to contract. The structural and contractile unit of myofibrils is the sarcomere. 1. Structure of the MSS Myofibrils, which give cells a striated appearance under the microscope (hence the name striated muscle cells), are formed of long filamentous proteins forming a cytoskeleton: these are thin actin myofilaments and thick myosin myofilaments. These protein filaments are associated with each other in such a way that each myosin filament is surrounded by several actin filaments. The sliding of the two types of filaments relative to each other allows the shortening of the sarcomere and therefore the contraction of the muscle fiber. Structural description of muscle: Functional unit of muscle Skeletal striated muscle is a heterogeneous tissue. The functional unit of muscle is the motor unit, which is defined as the assembly consisting of a motor neuron and the muscle fibers it innervates. 2. Contractile proteins of striated skeletal muscle Figure 2 showsof a sarcomere of a muscle cellstriated. Figure2: Diagram of a sarcomere of a relaxed (top) or contracted (bottom) muscle cell 2  C. Excitation-contraction coupling Molecular mechanism of muscle contraction(Fig. 3):Contraction is only possible: If the cytosolic concentration of Ca2+ ions is sufficient.This Ca2+ is released into the cytoplasm following the arrival of action potentials which open ion channels in the sarcoplasmic reticulum which stores the Ca2+. If there is energy present, provided by the hydrolysis of ATP molecules Then the contraction mechanism is set in place: Ca2+ ions bind to actin and release the myosin binding site there. The myosin attaches and changes shape: its head pivots, which causes the actin to slide between the myosins. Myosin then binds ATP which causes it to detach from actin. The hydrolysis of ATP to ADP + Pi will allow the myosin head to pivot so that it is ready for further binding to actin. Figure3: Diagram of the muscle cell contraction mechanism Action potential and muscle contraction The conduction of the action potential of the motor nerve occurs in a saltatory manner from one node of Ranvier to the other.When the action potential reaches the nerve terminal, at the presynaptic membrane, voltage-gated calcium channels are activated, the entry of Ca2+ causes the release of acetylcholine into the synaptic cleft. The action of acetylcholine at the postsynaptic membrane will generate the muscle action potential. 1. Motor plate The neuromuscular junction is the set of synaptic contacts between the terminal arborization of a motor axon and a striated muscle cell (Fig. 4). The whole constitutes the motor endplate. It is formed by the juxtaposition of the terminal of a motor axon and the subsynaptic domain of the striated muscle fiber, these two elements are separated by a synaptic cleft. The synaptic cleft is occupied by a basement membrane containing the enzyme for the degradation of acetylcholine, acetylcholinesterase. The muscle plasma membrane is differentiated into a "motor endplate": it has numerous folds, carrying the postsynaptic acetylcholine receptors at the level of the crests. 3  1. Motor axon; 2. Schwann sheath; 3. Acetylcholine vesicles; 4. Synaptic cleft; 5. Mitochondria; 6. Myofibrils; 7. Nicotinic acetylcholine receptors Figure4: Structure of the neuromuscular junction The nicotinic receptor is a cation channel whose opening causes a rapid inward current. The binding of acetylcholine to the subunit causes the channel to open. The subunits Orhave the function of stabilizing the closed stage of the receiver. 2. Biochemical modifications D. Heat production and energy of contraction 1. Thermal and metabolic aspects ATP is necessary for muscle fiber contraction and relaxation to: the binding of ATP to myosin necessary for the dissociation of myosin heads from the actin filament; the hydrolysis of ATP which provides the energy necessary for the movement induced by the “rotation” of the myosin heads; ATP hydrolysis at the calcium-ATPase pump which allows relaxation by calcium recycling. In order to maintain contractile activity, ATP molecules must be supplied by metabolism as quickly as they are degraded by the contractile process. This is done by three major metabolic pathways: the anaerobic alactic pathway, the anaerobic lactic pathway, and the aerobic pathway. Skeletal Muscle Metabolism:ATP regeneration - During muscle contraction, the energy used for contractile activity (flexion, detachment of myosin heads and operation of the calcium pump) is provided by ATP. - Since ATP is the only energy source that can directly fuel contraction, and since immediately available ATP stores are small in the muscle, allowing a contraction of 4 to 6 seconds, ATP must be continuously replenished in order for contraction to continue. Regeneration takes place in 03 ways in a fraction of a second: 1- Interaction of ADP with creatine phosphate (CP): At the beginning of the contraction, once the low ATP reserves have been consumed, additional ATP is rapidly reconstituted from a high-energy molecule: Creatine phosphate (CP): PhosphoCreatine + ADP → Creatine + ATP. This reaction is catalyzed by Creatine Kinase. 2- Anaerobic glycolysis:Muscle glycogen stores are converted into lactic acid with the production of two (02) ATP molecules. Together, ATP and creatine phosphate stores and aerobic glycolysis can sustain muscle activity for one minute. 4 3- Aerobic cellular respiration: oxidative phosphorylation:During light but prolonged muscular activity, the ATP used by the muscles is provided by aerobic cellular respiration which takes place in the mitochondria and requires the presence of oxygen and involves a series of chemical reactions (Krebs cycle, respiratory chain and electron transport). During aerobic respiration, glucose is completely degraded; the complete oxidation of one glucose molecule provides 36 ATP molecules. 2. Muscle fatigue Fatigue results in decreased physical performance. Muscle fatigue involves a component: metabolic and ionic peripherals: endocrine central. 2.1. Metabolic component of fatigue Metabolic factors of fatigue evolve according to the duration and intensity of muscular exercise. For short, intense workouts, 02 elements contribute to the reduction of the contractile capacities of the skeletal muscle which are: - modulation of phosphagen reserves - changes in ionic balances. For the metabolic component of fatigue, it is essentially: - intramuscular accumulation of inorganic phosphorus, - increased extracellular potassium - decreased Ca2+ reuptake. For longer efforts the main factor in fatigue is the reduction in muscle glycogen reserves which plays a role both in the continuation of a single exercise carried out until exhaustion and in chronic fatigue resulting from intense training. These phenomena result in a reduction in the contractile capacity of skeletal muscles. The mechanisms are different depending on the duration and intensity of the muscle contraction. For very prolonged effortsthe decrease in glycogen reserves stimulates the use of other sources of substrates including amino acids. In terms of mechanism,It is likely that the decrease in carbohydrate energy flow during muscle contraction increases nitrogen mobilization through the purine nucleotide cycle. This results in increased ammonia production, which is another factor in muscle fatigue. This increase in ammonia stimulates hepatic ureogenesis and uric acid production. 2.2.Endocrine component of fatigue All anterior pituitary functions are altered by overtraining. 2.2.1. Hypothalamic-pituitary-testicular axis Under the effect of fatigue: - In males:a decrease in plasma testosterone concentration; - In females:Menstrual cycle disruption is associated with decreased progesterone production in the second phase of the cycle and a short luteal phase. Mechanism of action related to overtraining and inhibition of steroid hormone synthesis. This phenomenon appears to be partly dependent on an increase in endorphins and CRH (corticotropin releasing hormone) in the central nervous system resulting from stress leading to a decrease in the release of pituitary gonadotropins (LH and FSH) and the sensitivity of Leydig cells to LH, thereby decreasing testosterone production. 2.2.2. Somatotropic axis Fatigue induces a decrease in the somatotropic response. 2.2.3. Corticotropic axis and sympatho-medullary adrenal system The secretion of catecholamines and hormones of the hypothalamic-pituitary-adrenal complex is an integral part of the physiological response to exercise. 5 Both axes are also involved in the recovery phase of exercise. Upon cessation of exercise, plasma catecholamine concentrations return to their pre-exercise concentration within a few minutes of cessation of exercise. There is usually a delay between cessation of exercise and the return of cortisol to its resting values. 2.3. Central component of fatigue Effects of fatigue on the nervous control of contraction:Firstly, this fatigue results from a reduction in stimulation at the peripheral motor neuron level, but also from a reduction in motor control at the cortical level. 3. Rigor mortis After death,Chemical breakdown in muscle fibers allows Ca2+ to exit the sarcoplasmic reticulum. The Ca2+ binds to tropin and triggers filament sliding. However, because ATP synthesis has ceased, the myosin cross- bridges cannot detach from actin.The resulting state, in which muscles are rigid (cannot contract or stretch), is called rigor mortis. It lasts about 24 hours, then disappears after another 12 hours as tissues begin to disintegrate. II/ Smooth muscle a. Structure of smooth muscle - Present in the wall of most hollow organs of the body such as the airways, vessels, digestive and genitourinary systems. Each smooth muscle fiber is a spindle cell that contains a single nucleus (Fig. 5), the diameter of these small fibers is between 2 and 4 um. - Smooth muscle fibers do not have elaborate nerve endings like those found in skeletal muscles, but they are connected to neurofibers of the autonomic nervous system. - The sarcoplasmic reticulum of smooth muscle fibers is less developed than that of skeletal muscle fibers so there are no transverse tubules T. - Smooth muscles do not have transverse striations, although they do contain thick and thin filaments, but these filaments are different from those found in skeletal muscles: - Thick and thin filaments are not arranged in sarcomeres - The thick filaments of smooth muscle carry myosin heads along their length, a feature that allows these muscles to be so powerful. - Tropomyosin is associated with thin filaments but not troponin. Figure5: Structure of smooth muscle b. Excitation-contraction coupling in smooth muscle The contraction mechanism of smooth muscles is similar to that of skeletal muscles in the following ways: - Myofilament sliding is due to the interaction of actin and myosin - Contraction is triggered by increased intracellular calcium ion concentration - Myofilament sliding requires ATP. 6 The stages of muscle contraction: - During excitation-contraction coupling, Ca2+ is released from the sarcoplasmic reticulum, but it also enters from the interstitial fluid - To activate myosin, Ca2+ interacts with regulatory proteins: calmodulin located on myosin filaments and a kinase called Myosin Light Chain Kinase (MLCK), - And since thin filaments have no troponin to mask the binding site of the myosin heads, they are always ready to contract - Ca2+ binds to calmodulin and the calcium-calmodulin complex binds and activates myosin light chain kinase (MLCK). - The activated kinase hydrolyzes ATP and phosphorylates myosin, allowing it to interact with actin: shortening occurs. - Like skeletal muscles, smooth muscles relax when the intracellular Ca2+ concentration decreases. 7