Muscle Physiology PDF 2025 by Dr. Mohammed EL-SHERIF

2025 BY Dr. Mohammed EL-SHERIF  Muscle Physiology Physiology of the Muscle Muscle is a tissue that shortens and develops tension leading to movement. Muscles are divided into: (Fig 35) 1) Striated muscles: skeletal and cardiac muscles, characterized by alternating l...

2025 BY Dr. Mohammed EL-SHERIF  Muscle Physiology Physiology of the Muscle Muscle is a tissue that shortens and develops tension leading to movement. Muscles are divided into: (Fig 35) 1) Striated muscles: skeletal and cardiac muscles, characterized by alternating light and dark bands. 2) Smooth muscles have no distinguishing surface. Approximately 40% of the body is skeletal muscles, and l0% is smooth and cardiac muscles. Fig 35: Skeletal, cardiac, and smooth muscles. Skeletal Muscles: The skeletal muscles are attached to the bones in which the human body contains over four hundred voluntary skeletal muscles, their contraction depends on their nerve supply. Skeletal muscle performs four major functions: 1) Force production for locomotion and breathing. 2) Force production for maintaining posture and stabilizing joints. 3) Heat production. 4) Help venous drainage. Dr. EL-SHERIF 2  Muscle Physiology Morphology: (Fig 36 and 37) The skeletal muscle is made up of muscle fibers bundled together by connective tissues and arranged in parallel. Each muscle fiber is a single cell which is enveloped by the cell membrane called the sarcolemma. The muscle fiber is made of many parallel myofibrils. The Myofibrils are composed of two major contractile proteins thick filaments composed of the protein myosin and thin filaments composed primarily of the protein actin. The arrangement of these two protein filaments gives skeletal muscle its striated appearance. Fig 35: The structure of a skeletal muscle. Fig 36: The structure of a skeletal muscle fiber. The sarcomeres: The myofibrils are divided into functional units called sarcomeres by transverse protein sheet called Z lines. Dr. EL-SHERIF 3  Muscle Physiology Myosin (thick) filaments are arranged in the middle of each sarcomere. While Actin (thin) filaments are attached from one end to the Z line while the other end overlaps a part of the thick filaments. Titin (elastic protein) attaches the thick filaments to Z line (Fig 37 and 38). Titin helps keep the thick filaments centered; it also helps the muscle fiber resist extreme stretching. Fig 37: The structure of a sarcomere Fig 38: Changes in the Appearance of a Sarcomere during contraction Banding Pattern [Cross Striations]: (Fig 37 and 38) Light microscopic views of skeletal muscle show striations: a) A-bands: dark areas in the center of the sarcomere that contain Myosin. Myosin and actin overlap to some extent in the A band. b) I-bands: light areas on either side of the Z disk that contain Actin. · c) H-zone: area of the A band without actin (myosin only). During muscle contraction, each sarcomere shortens, the I-bands and H-zones become narrower, while the A-bands does not change. Dr. EL-SHERIF 4  Muscle Physiology Tubular System: (Fig 39) 1 The Transverse (T) Tubule: It is an invagination of the surface of the muscle fiber membrane that contains extracellular fluid. Its membrane contains a voltage-sensitive dihydropyridine (DHP) receptor. The action potential spreads over the surface of the muscle fiber membrane and is propagated into the network of T- tubules. 2 The Sarcoplasmic Reticulum (SR): It is the endoplasmic reticulum of the muscle fiber that surrounds each myofibril and runs parallel with it. Its ends expand to form terminal cistemae (TC) in contact with T tubules. It has a high concentration of Ca++. The SR membrane contains a ryanodine receptor which are Ca++ channels and contain foot processes which are small projections between the SR and T-tubule membranes. N.B. Excitation of T-tubule by action potential activates the voltage-sensitive dihydropyridine (DHP) receptor on T-tubules that opens the ryanodine Ca2+ channel on the SR leading to rapid Ca++ release and hence rapid contraction of all the myofibrils. Fig 39: The dihydropyridine (DHP) receptor on the T tubule functions as a voltage sensor Dr. EL-SHERIF 5  Muscle Physiology The Muscle Proteins: A Myosin Protein: (Fig 40): Each myosin molecule is made up of 2 heavy chains and 4 light chains. The two heavy chains form a helix; their terminal portions with the 4 light chains form 2 arms and globular heads called cross bridges. The heads contain an actin-binding site, ATP binding site, and ATP ase site. Cross-bridges are flexible at two points called hinges: one hinge between the arm and the body, and the second between the arm and the head. Fig 40: Structure of myosin molecules B Actin Protein: (Fig 41): Each actin molecule is formed of two chains coiled as a helix. Actin has a specific site for myosin (active site). At rest, Tropomyosin molecules cover the active sites on the actin. Troponin molecules are small globular proteins and attach the tropomyosin to actin. Troponin molecule is formed of: 1) Troponin I: has a strong affinity for actin and binds with it. 2) Troponin T has a strong affinity for tropomyosin and birtds with it. 3) Troponin C has a strong affinity to Ca2+. When Ca2+ combines with troponin C, this will initiate the contraction process. Fig 41: Structure of actin molecules Dr. EL-SHERIF 6  Muscle Physiology Activation of the Skeletal Muscle Neuromuscular Transmission: Definition: Transmission of nerve impulses from alpha motor neuron to skeletal muscle fibers. Physiologic Anatomy of Neuromuscular Junction: The alpha motor neuron branches as it approaches the muscle, sending axon terminals (end feet) to several skeletal muscle fibers. Each skeletal muscle fibres receives only one axon terminal containing acetylcholine (Ach) vesicles. The nerve ending fits into depression in the muscle membrane. Underneath the nerve endings the muscle membrane is thickened and called motor end plate (MEP) which is rich in Acetylcholine receptors and contains numerous junctional folds (Fig42). The extracellular space between the nerve terminals & muscle membrane is called Synaptic cleft. It is occupied by connective tissue called basal lamina, to which the enzyme acetylcholine esterase is bound. Fig 42: The neuromuscular junction Dr. EL-SHERIF 7  Muscle Physiology Sequence of Events during Neuromuscular Transmission: 1) Arrival of nerve impulse at nerve ending opens voltage-gated Ca++ channels. 2) Ca2+ enters the nerve endings and causes rupture of vesicles and exocytosis of acetylcholine. 3) Acetylcholine crosses the synaptic cleft and binds to its receptor (which is a ligand-gated channel) in the MEP. (Fig43) 4) The channel is opened and leads to Na+ ions influx and depolarization of MEP. The response is called end-plate potential (EPP). 5) The EPP is a graded, non -propagated response that acts as a stimulus and depolarizes the adjacent muscle membrane to its firing level. Thus, the EPP depolarizes the muscle membrane to threshold. 6) Action potentials are generated on either side of the end plate and are propagated in both directions along the muscle fiber. The muscle action potential in turn initiates muscle contraction. 7) Acetylcholine then dissociates from its receptor and is hydrolyzed by acetylcholine esterase in the synaptic cleft. Degradation of acetylcholine is necessary to prevent it from causing multiple muscle contractions. N.B. Later in time, new vesicles are formed from invaginations of the presynaptic membrane. These vesicles are refilled and used again to discharge acetylcholine. Fig 43: Neuromuscular transmission Dr. EL-SHERIF 8  Muscle Physiology Properties of Neuromuscular Transmission: 1) Unidirectional: it occurs in one direction only from the nerve to the muscle. 2) Delay of about 0.5 msec: It represents the time needed for the release of acetylcholine, change in the permeability of muscle fiber membrane, inflow of Na+ and building up of depolarization to the firing level. 3) Fatigued easily due to repeated stimulation and exhaustion of acetylcholine vesicles. 4) Effect of Ions: a. Ca++ entry into the end feet causes rupture of the vesicles containing acetylcholine. b. Excess Mg++ competes with Ca++ and the release of acetylcholine is greatly decreased. 5) Effect of drugs: a. Drugs that stimulate neuromuscular transmission by acetylcholine-like action: These drugs are not destroyed by cholinesterase and their action persists for many minutes to several hours. e.g. methacholine, carbachol, and nicotine in small dose. b. Drugs which stimulate neuromuscular transmission by inactivating cholinesterase: e.g. neostigmine, physostigmine, and di-isopropyl fluorophosphate. Thus, extreme amounts of acetylcholine can accumulate and then repetitively stimulate the muscle fiber. c. Drugs that block neuromuscular transmission (curariform drugs): Curare competes with acetylcholine for the receptor sites on the membrane. Dr. EL-SHERIF 9  Muscle Physiology Myasthenia Gravis: Myasthenia gravis is a serious and sometimes fatal disease in which skeletal muscles are weak and tire easily. Muscle paralysis may occur due to inability of the neuromuscular junctions to transmit enough signals from the nerve fibers to the muscle (Fig 44). It is an autoimmune disease due to antibodies against acetylcholine receptors. In severe form of the disease, the patient dies of respiratory muscles paralysis. The disease can be treated by administration of anticholinesterase drugs, such as neostigmine to accumulate adequate amounts of acetylcholine. Fig 44: Myasthenia Gravis Miniature End-Plate Potential: At rest, a few vesicles containing acetylcholine rupture spontaneously and release their content. This produces a minute depolarization at the motor end plate. Dr. EL-SHERIF 10  Muscle Physiology Changes Following Skeletal Muscle Stimulation A Electrical Changes Following Skeletal Muscle Stimulation: The electrical events in skeletal muscle and the ionic fluxes underlying them are like those in nerve with some differences: The resting membrane potential of skeletal muscle is about - 90m V. The action potential lasts 2- 4 ms Is conducted along the muscle fiber at about 5 m/sec. The action potential precedes the contraction by about 2 msec (Fig 45). Fig 45: The electrical and mechanical responses of a mammalian skeletal muscle fiber to a single maximal stimulus. B Excitability Changes Following Skeletal Muscle Stimulation: During the action potential, skeletal muscle fiber is refractory to re-stimulation. As the action potential precedes the muscle contraction, thus once the muscle begins to contract, it has regained its excitability and can respond to re-stimulation (can be tetanized). C Mechanical Changes Following Skeletal Muscle Stimulation: Molecular Mechanism of Muscle Contraction: Excitation-Contraction (EC) Coupling (Fig.46): It is the process by which an action potential of muscle fiber initiates the contractile process. Dr. EL-SHERIF 11  Muscle Physiology 1) Release of Ca2+: The propagation of the action potential into the T -tubule causes the Ca2+ channels on the terminal cisternae (TC) to open. Ca2+ flows out of the TC and into the cytoplasm. 2- Activation of muscle proteins: Ca2+ binds to troponin-C on actin. Troponin undergoes a conformational change in which tropomyosin moves away from its position covering the myosin-binding site on actin. Once uncovered,’ the binding site on actin combines with the myosin cross-bridges and contraction begins. 3- Generation of tension: Tension is the developed force when a muscle contracts. It is generated by the cycling of the cross-bridges as follows: (fig 47) a. Binding of actin and myosin occurs spontaneously, after Ca2+ binds to troponin C and tropomyosin moves away from actin active sites. b. Bending of the cross-bridges and the sliding of actin filament across the myosin filament. The energy used to phosphorylate the cross-bridge and generate tension is obtained from hydrolysis of ATP by ATPase enzyme into adenosine diphosphate (ADP) and inorganic phosphate (Pi). Both ATP and ATPase are attached to the cross-bridge. c. Detachment of the cross-bridge from actin. For detachment to occur, ADP and Pi must be removed from the cross-bridge and a new molecule of ATP put in their place. This new ATP reduces the affinity of the cross bridges for the active site. If no ATP is available, the thick and thin filaments cannot be separated (Muscle contracture). d. Return of the cross-bridge to its original upright position to participate in another cycle. Cycling continues as long as Ca2+ is attached to troponin C and energy {ATP) is available. The force developed by the bending of the cross-bridge is transmitted through the actin filament to the Z disk and then through the sarcolemma and tendinous insertions of the muscle to the bones. Dr. EL-SHERIF 12  Muscle Physiology 4) Relaxation: Occurs when the Ca2+ is removed from the cytoplasm by Ca2+ pump located on the SR membrane. When the intracellular Ca2+ concentration falls: Troponin returns to its original conformational state. Tropomyosin moves back to cover the myosin binding site on actin. Cross-bridge cycling stops. Fig 47: Cycling of cross bridges. The All or None Law: A single skeletal muscle fiber obeys all or none law in which the skeletal muscle fiber contracts maximally or does not contract at all. A threshold stimulus produces maximal contraction provided that the experimental conditions remain the same. The Muscle Twitch: (Fig 45) It is a brief contraction followed by relaxation due to a single action potential. The twitch starts about 2msec after the depolarization of the membrane. Dr. EL-SHERIF 13  Muscle Physiology Types of Skeletal Muscle Contraction The skeletal muscles contain, in addition to the contractile element, elastic and viscous elements in series with the contractile element and present mainly in the tendons (series elastic component) (Fig 49). 1 Isometric contraction: An isolated skeletal muscle is fixed to a holder at one end and a heavy load is attached to its lower end (Fig 49). The load is allowed to stretch the muscle to a certain degree then a support surface is placed below the load to prevent any more stretch of the muscle. Now, if the muscle is stimulated to contract against the heavy load, it will not be able to shorten because the load is too heavy for the muscle. However, sarcomeres within the myocytes do shorten leading to stretching of the series elastic elements within the muscle (Fig 49). Tension inside the muscle rises to its maximum while the length of the whole muscle remains constant. (Fig 50). Fig 49: Series elastic element (SE) and contractile element (CE) during an isotonic contraction (A) and an isometric contractile (B). 2 Isotonic contraction: A smaller load is attached to the isolated skeletal muscle (Fig 49). The muscle is allowed to stretch to the same degree before the load is supported by a surface below. When the muscle is stimulated, contraction will start isometric and muscle tension rises till the tension reaches a level that can lift the load. Now the muscle will be able to shorten while holding the small load. Dr. EL-SHERIF 14  Muscle Physiology Tension remains constant while the muscle shortens. (Fig 51) Muscle contraction starts isometric till it generates enough tension to overcome the load, then contraction continues as isotonic, and the muscle shortens. If the load is too large, the maximum tension developed by the muscle. In isometric contraction is not sufficient to lift the load. N.B. With heavier loads: a) The duration of isometric contraction phase is longer. b)The rate and extent of muscle shortening during isotonic contraction is less. Fig 50: Characters of isometric contraction Fig 51: Characters of isotonic contraction Dr. EL-SHERIF 15  Muscle Physiology Basic differences between isometric and isotonic contractions: Isometric contraction Isotonic contraction Tension changes Increases Constant Length changes Constant Shorten Sliding of myofibrils Less sliding More sliding along each other Duration Lasts shorter Lasts longer Needs less energy since Needs greater energy since Energy need the load is not moved the load is moved a distance No external work is done External work is done since Work done since the load is not moved the load is moved a distance Mechanical efficiency= Zero 20-25%. o/o of energy input converted into work Examples Tension of a part of the Movement of part of the body and maintenance of body or the body as a whole: posture against gravity When When a person lifts a heavy standing, person tenses the weight using the biceps, the quadriceps muscles to contraction starts isometric tighten the knee joints and to and completed isotonic. keep the leg stiff. During running, contractions are a mixture of isometric when the legs hit the ground; and isotonic to move the limbs Dr. EL-SHERIF 16  Muscle Physiology Factors Affecting Skeletal Muscle Contraction I Type of muscle fibers: (Fig 52) Human skeletal muscles contain mainly 2 types of muscle fibers: 1) Slow Fibers (Red= type I) characterized by the following: Small muscle fibers are innervated by small slowly conducting motor neurons. Contain large numbers of oxidative enzymes (high mitochondrial volume). Have low ATPase activity. Surrounded by more extensive capillaries to supply extra amounts of oxygen. Contains a higher concentration of myoglobin, which stores oxygen until need. These characters provide type I fibers with slow contractile mechanism and large capacity for aerobic metabolism and a high resistance to fatigue. 2) Fast Fibers (pale = type II b) characterized by the following: Larger fibers innervated by large rapidly - conducting motor neurons. Contain extensive sarcoplasmic reticulum for rapid release of calcium ions. Have large amounts of glycolytic enzymes for rapid release of energy by the glycolytic process. Have high ATPase activity. Contain less blood supply, less myoglobin content, and fewer mitochondria. These characters provide type II b fibers with rapid contractile mechanisms and less resistance to fatigue. Fig 52: Is a myogram, or graph of twitch tension development in skeletal muscle fibers from various muscles. Dr. EL-SHERIF 17  Muscle Physiology N.B. 1) Most muscles of the body contain both types of muscle fibers. 2) Muscles adapted for long posture-maintaining contractions e.g. back muscles & soleus muscle are composed mainly of slow fibers. Muscles specialized for fine skilled movements e.g. external ocular muscles & some hand muscles are composed mainly of fast fibers. 3) Muscle groups with a high percentage of fast fibers exert more force and a greater velocity than those with predominant slow fibers. 4) Aging is associated with a loss of muscle mass. Aging results in a loss of fast fibers and a relative increase in slow fibers. II Stimulus Factors (Grading of muscle contraction): Motor unit: The axon of spinal motor neuron branches to supply several muscle fibers. The motor neuron and the muscle fibers it innervates form a motor unit (Fig 53). The number of muscle fibers in motor unit varies. In muscles which perform fine, graded and precise movements e.g. hand muscles and ocular muscles, each motor unit contains few muscle fibers 3-6 muscle fibers. In big muscles which perform gross movements e.g. muscles of the leg and back each motor unit contains 100-200 muscle fibers. Fig 53: the motor unit Dr. EL-SHERIF 18  Muscle Physiology 1) Strength of the stimulus: Increasing the strength of stimulus will increase the number of activated motor units [recruitment] with gradual increase in whole muscle response. Maximal stimulus activates all motor units including all muscle fibers. Supra maximal stimulus would not give further response as each fiber responds maximally according to all or none law. 2- The frequency of muscle stimulation: (Fig 54) The force of contraction can be increased by increasing the frequency of muscle stimulation because more Ca2+ is released from the sarcoplasmic reticulum each time the muscle is stimulated. With rapidly repeated stimulation, repeated contractions with incomplete relaxation have occurred which is called incomplete tetanus or clonus. If the repeated contractions fuse into one continuous contraction with no relaxation it is called complete tetanus. During a complete tetanus, the tension developed is about 4 times that developed by the individual twitch contractions due to accumulation of free calcium ions in the myofibrils i.e. continuous cycling of the cross-bridges. Treppe (Staircase Phenomenon): is the progressive increase in the magnitude of separate twitch contraction of skeletal muscle to a plateau value during repetitive stimulation after a period of rest. This phenomenon is explained by the persistent elevated levels of free Ca2+ in the cytoplasm. Fig 54: (a) Treppe: increase in peak tension with each successive stimulus after the completion of the relaxation phase of the preceding twitch. (b,c) Incomplete tetanus (relaxation phase is not completed). (d) Complete tetanus with high frequency (relaxation phase is eliminated). Tension plateaus at maximal levels. Dr. EL-SHERIF 19  Muscle Physiology Grading of muscular activity: a) With minimal voluntary activity, a few motor units discharge, and with increasing voluntary effort more units contract, this process is called recruitment of motor units. b) The force of a voluntary movement is also increased by increasing the frequency of discharge of impulses to the motor unit leading to tetanic contractions. During voluntary movements of moderate intensity, the rate of discharge of impulses to the motor units would produce clonic contractions. The motor units contract asynchronously, the responses of the various motor units merge into a smooth contraction of the whole muscle (Fig 55). Fig 55: Two motor unit A and B show subtetanic contractions (clonus). Asynchronous discharge of both units will lead to smooth contraction of greater force (C). III Length-tension relationship: Fig (56) There is a relationship between the initial muscle fiber length (preload) and the active tension developed during its isometric contraction. Length-tension relationship measures tension developed during isometric contractions when the muscle is set to fixed lengths (preload). Preload is the load that a muscle experiences before the onset of contraction. a. Passive tension is the tension developed by stretching the muscle to different lengths (without stimulation). b. Total tension is the tension developed when the muscle is stimulated to contract at different lengths. c. Active tension is the difference between total tension and passive tension. Fig 56: Lengthtension relationship for the human triceps muscle. Dr. EL-SHERIF 20  Muscle Physiology The effect of Sarcomere length on active tension (Fig 57): a) Maximal force is obtained when the muscle fiber length is set at a sarcomere length of 2.2 μ. This is the resting length of the muscle inside the body. At this length, the overlap between thick and thin filaments is optimal, since every cross-bridge from the thick filament is opposite an actin molecule. b) Increasing the sarcomere length more than 2.2 μ causes a decrease in the force development. At this condition, the overlap between thick and thin filaments is decreased. Thus, some cross-bridges do not have actin filaments to bind with. c)Decreasing the sarcomere length below 2.2 μ causes a decrease in force development. At this condition, the ends of the two actin filaments overlap each other, in addition to overlapping the myosin filaments, making it more difficult for the muscle to develop force. Fig 57: Effect of Sarcomere Length on Active Tension Dr. EL-SHERIF 21  Muscle Physiology IV Load-Velocity Relationship: (Fig 58) For the muscle to shorten during isotonic contraction, it must lift a weight, called afterload. Afterload is the load encountered by the muscle only after it starts to contract. Increasing the afterload has the following effects: a) The velocity of shortening decreases as the afterload increases because each cross-bridge cycle takes longer time. b) The amount of shortening decreases as the afterload increases. c) The maximal velocity of shortening (V-max) occurs when there is no external load (zero load). N.B. V-max is theoretical because load cannot be zero. Fig 58: Relation of load to velocity of contraction in a skeletal muscle V Muscle Fatigue: Prolonged and strong contraction of a muscle leads to a state of muscle fatigue, which decreases the strength of contraction, prolongs its duration, and relaxation becomes incomplete [contracture]. This effect is due to: a) Accumulation of metabolites, such as lactic acid which increases intracellular acidity. b) Depletion of muscle ATP, glycogen, and creatine phosphate. c) Diminished transmission at neuromuscular junction. d) Interruption of blood flow through a contracting muscle and loss of nutrient supply, especially loss of oxygen. Dr. EL-SHERIF 22  Muscle Physiology D- Metabolic Changes Following Skeletal Muscle Stimulation: Energy Sources and Muscle Metabolism: I) During Rest: The skeletal muscles consume energy for: a. Maintenance of the resting membrane potential. b. Synthesis of chemical substances e.g. glycogen. c. Production of Muscle tone. II) During Contraction: Energy consumption is markedly increased. ATP is the only immediate energy source for the contraction of muscle. ATP is hydrolyzed anaerobically into ADP and the muscle protein myosin acts as the enzyme adenosine tri-phosphatase (ATPase) Myosin ATP+ H2 ATPase ADP+ H3 PO4 + E 1200 Cal. ATP inside the muscle can provide energy for maximal contraction for 5-6 seconds. ATP is reformed continuously by means of three different metabolic mechanisms: (1) Phosphocreatine; (phosphagen system) Crearine~ po3 Most muscle cells have two to three times as much phosphocreatine as ATP. Energy transfers from phosphocreatine to ATP within a small fraction of a second. The cell phosphocreatine plus its ATP are called the phosphagen energy system Together they can provide maximal muscle power for a period of 10-15 seconds, enough for 100 m run. · ADP + creatine phosphate ATP + creatine Creatine phosphate is later restored by means of the reverse reaction during muscle relaxation. Dr. EL-SHERIF 23  Muscle Physiology (2) The Glycogen lactic Acid system: The glycogen - lactic acid system can provide 30 to 40 seconds of excess muscle activity in addition to the 10 to 15 second provided by the phosphagen system. Glucose+ 2ATP [or glycogen + 1 ATP] Anaeroic 2 lactic acid+ 4 ATP. Glycolysis in cytoplasm Lactic acid causes extreme fatigue which serves as a self-limitation to further use of this system for energy. Removal of the lactic acid from all the body fluids requires an hour or more: a- Some of the lactic acid is converted to pyruvic acid then metabolized oxidatively by all the body tissues. b- Much of the lactic acid is reconverted by the liver into glucose used mainly to replenish the glycogen stores of the muscles. c- It is used as a fuel in the heart. (3) The Aerobic System: The aerobic system means the oxidation of foodstuffs (glucose, fatty acids, and amino acids) in the mitochondria to provide energy. Glucose+ 2 ATP [or glycogen+ 1 ATP] oxygen 6 C02 + 6 H20 + 38 ATP Free fatty acids oxygen C02 + H20 + ATP Comparing the 3 systems for endurance, the relative values are: Phosphagen system 10-15 seconds Glycogen-lactic acid system 30-40 seconds Aerobic system Unlimited time “as long as nutrients and 02 are available. N.B. The phosphagen system is the one utilized by the muscle for power surges. The aerobic system is required for prolonged athletic activity. Glycogen-lactic acid system is important for giving extra power during intermediate races (200 to 800-m runs). Free fatty acids are the major substrate for muscle at rest & during recovery from contraction. Dr. EL-SHERIF 24  Muscle Physiology III) During recovery (oxygen Debt): During muscular exercise, the muscle blood vessels dilate, and blood flow is increased so that the available 02 supply is increased. Up to a point, the increase in 02 consumption is proportionate to the energy expended, and all the energy needs are met by aerobic processes. When muscular exertion is very great, some ATP is provided by the anaerobic pathway, when ATP, CP stores and 02 supply from myoglobin are depleted. After a period of exertion is over, the rate of ventilation remains high for some time, extra 02 is consumed to remove the excess lactate, replenish ATP and CP stores, and replace 02 that have come from myoglobin. This extra post-exercise 02 consumption is called [oxygen debt]. It is measured experimentally by determining 02 consumption after exercise until a constant basal consumption is reached and subtracting the basal consumption from the total. Electromyography: Electromyography is a record of the electrical activity of the muscle using a cathode ray oscilloscope (Fig 59). Electrical activity is picked up by metal disc electrode placed on the skin overlying the muscle or by hypodermic needle electrodes inserted in the muscle. Fig 59: Electromyogram recorded during contraction of the gastrocnemius muscle. Muscular hypertrophy: It is the increase in size of muscle as a result of forceful muscular activity. The number of muscle fibers in the muscle, does not change while the muscle fibers increase in thickness, in total number of myofibrils, and in their content of ATP, creatine phosphate, and glycogen. Dr. EL-SHERIF 25  Muscle Physiology Reaction of muscle to denervation: If the nerve supply to the muscle is injured, the muscle is paralyzed. This is known as lower motor neuron lesion: a) Muscle atrophy is a decrease in muscle size and the muscle fibers are replaced gradually by fibrous tissue. b) Muscle fasciculation: It is spontaneous contractions of motor units sufficient to be seen under the skin that occurs immediately after motor nerve damage. As the nerve fibers degenerate, spontaneous impulses are discharged during the first few days. Electromyographic records can be picked by metal disc electrodes placed on the skin overlying the paralyzed muscles. c) Muscle fibrillation: Spontaneous contractions of separate muscle fibers occur after complete degeneration of the motor nerve fibers. It is due to denervation hypersensitivity that leads to spontaneous discharges of impulses due to increased sensitivity of denervated muscle to circulating acetylcholine It cannot be seen under the skin. Electromyographic records can be picked only by needle electrodes inserted in the muscle. Rigor Mortis: Several hours after death all the muscles of the body go into a state of contracture and become rigid even without action potentials. It is caused by loss of ATP, which is needed to produce separation of actin and myosin filaments during the relaxation process. The muscles remain in rigor until the muscle proteins are destroyed as a result of bacterial putrefaction 15-25 hours later. Rigor mortis is of medicolegal importance as it helps in the determination of time of death. Dr. EL-SHERIF 26  Muscle Physiology SMOOTH MUSCLES Smooth muscles are involuntary muscles found in blood vessels and viscera and innervated by autonomic nerve fibers. They differ greatly from striated muscles in structure, excitation contraction coupling and in mechanical properties. Smooth muscles play a variety of roles in various body systems; mainly they regulate the movement of materials along internal passageways. Types: Smooth muscle can be divided into: (fig 60) Visceral Smooth Muscle Multi-unit smooth muscle Occurs in large sheets and has Is made up of individual units 1 “gap junctions” between the without interconnecting bridges. individual muscle cells. Action potentials spread from one Action potential can’t spread from 2 fiber to the adjacent ones very easily one fiber to the adjacent fibers. i.e. functions as a syncytium. The whole muscle acts as one unit The muscle behaves like separate 3 i.e. obeys All or None Law. motor units. Single muscle fiber obeys All or None Law The muscle is superficially The muscle is densely innervated, 4 innervated, and it is spontaneously and contraction is under neural active and controlled by hormones, control (Fig 61). chemicals and neurotransmitters. Is found mainly in the walls of Is found in the ciliary muscle and the 5 hallow viscera e.g. gut, ureters and iris of the eye, vas deferens and many blood vessels. erector pili muscles of the skin. Fig 60: a. Singleunit (visceral) smooth muscle. b. Multiunit smooth muscle. Dr. EL-SHERIF 27  Muscle Physiology Fig 61: Innervation of smooth muscles Structure Characteristics of Smooth Muscle Tissue: (Fig 62) 1) Smooth muscles are not divided into sarcomeres with interdigitating thick and thin filaments, so they lack striations. Thick and thin filaments are dispersed throughout the cell. Cross-bridges extend from myosin and cycle similar to that of striated. 2) No troponin; instead there is calmodulin protein. 3) The sarcoplasmic reticulum is poorly developed. 4) T tubules are absent since the fibers are small enough that surface stimulus can activate the contractile process. 5) The thin filaments are attached to dense bodies. Some of these bodies are anchored to the cell membrane, but most are floating within the cytoplasm, connected to each other by intermediate filaments. Dr. EL-SHERIF 28  Muscle Physiology Electrical Activity of Smooth Muscle: Membrane Potentials and Action Potentials in Smooth Muscle: The membrane potential in smooth muscle is unstable and in relative resting states it averages about -50 to 60 mV. Superimposed on the membrane potential are waves of various types (An example of these waves is the slow waves of the gut) (Fig 63). These waves are not action potentials and cannot cause muscle contraction, but when the potential of the wave reaches the level of about -35 mV, an action potential is elicited and s reads over the muscle. Fig 63: A- Typical smooth action potential (spike potential). B- Repetitive spike potentials on top of slow rhythmical waves. C- Pace maker potential. D- An action potential with plateau. Action potentials of smooth muscle occur in 2 different forms: 1) Spike potentials: Such action potentials may occur in either similar form as in skeletal muscle or on top of slow waves or rhythmically [pacemaker potential]. The duration of the spike is about 50ms. 2) Action Potential with Plateau: Depolarization is similar to that of the typical spike potential. Repolarization is delayed for several hundred to several thousand milliseconds. Plateau is important for the prolonged contraction in some types of smooth muscles. Dr. EL-SHERIF 29  Muscle Physiology Role of Calcium Channels in Generating Smooth Muscle Action Potential: The cell membrane of smooth muscle has more voltage-gated calcium channels, but very few voltage-gated sodium channels. Therefore, flow of Ca2+ into the muscle fiber is mainly responsible for the action potential. However, Ca2+ channels open many times more slowly than do Na+ channels. This accounts for the slow action potentials in smooth muscle fibers. Excitation-Contraction Coupling of smooth muscle: (Fig 64) 1) Depolarization of the cell membrane opens voltage-gated Ca++ channels and Ca++ flows into the cell down its electrochemical gradient. 2) The Ca++ that enters across the cell membrane may cause release of additional Ca++ from the sarcoplasmic reticulum through Ca++ gated Ca++ channels. 3) Hormones and neurotransmitters also may open a cell membrane ligand-gated Ca++ channel or release Ca++ from the sarcoplasmic reticulum through lP3-gated Ca++ channels. 4) Intracellular [Ca++] increases. 5) Ca++ binds to calmodulin “Ca++ binding regulating protein”. The calcium/calmodulin complex activates myosin light-chain kinase (MLCK), which phosphorylates the regulatory light chain on the head of the myosin molecule. This results in ATP hydrolysis and cross-bridge cycling. Fig 64: Role of calcium ions (Ca++) in contraction and relaxation of smooth muscle cell Dr. EL-SHERIF 30  Muscle Physiology 6) The phosphorylated cross-bridges continue to cycle until they are dephosphorylated by myosin-light chain phosphatase. The amount of active myosin at any time depends on the relative activity of the MLCK and the phosphatase. 7) Relaxation occurs when the intracellular Ca++ concentration falls by Ca++ pump that pumps Ca++ into the ECF and Ca++ pump that pumps the Ca++ into the sarcoplasmic reticulum. These pumps are slow in comparison to the fast SR pump in skeletal muscle. Thus, the duration of smooth muscle contraction is longer than that of skeletal muscle. 8. When the intracellular Ca++ concentration falls and the MLCK becomes inactive, the MLC phosphatase removes phosphate from the head of myosin and the cross-bridge cycle ceases. 9. However, the dephosphorylated cross-bridges remain attached to actin. These are called latch-bridges (Fig 65). Latch-bridges provide smooth muscle with the ability to maintain tone for long time with little energy consumption. Since the latch bridges do not cycle or cycle very slowly, they don’t use much ATP. 10. Smooth muscle contraction uses less ATP than skeletal muscle. Thus, it is fatigue resistant. Fig 65: Activated smooth muscle can exist in a phosphorylated and an unphosphorylated (latch) state. Dr. EL-SHERIF 31  Muscle Physiology Control of Contractions of Smooth Muscle: Smooth muscle is characterized by its tendency to give rise to spontaneous contractions which may occur in a rhythmic form (rhythmic contractions) or a tetanic form (Muscle tone ormaintained partial contraction). These occur even in isolated smooth muscle when there is no nerve supply. These spontaneous contractions of smooth muscle are, to some extent, controlled in the body by motor neurons which innervate the muscle and by a number of stimulatory factors acting directly on the smooth muscle and can initiate contractions via eliciting action potentials or even without action potential (Fig 66)· 1) Stretch: Visceral smooth muscle responds to stretch by contraction. This response allows a hollow organ to contract automatically and evacuate its contents when it is distended. 2) Local factors: Relaxing factors: acids, excess C02 and oxygen lack. Contracting factors; alkalis, excess K+. 3) Cold: increases the contraction of smooth muscles 4) Humoral Factors: ligand binds to its membrane receptors and results in: a. Excitatory receptors increase cytoplasmic Ca++ and cause contraction. b. Inhibitory receptors decrease cytoplasmic Ca++ & cause relaxation mediated by activation of K+ channels which inhibits Ca++ influx or increase in the active transport of Ca++. Dr. EL-SHERIF 32  Muscle Physiology 5) Role of Nerve Supply: Smooth muscle has a dual nerve supply from the 2 divisions of the autonomic nervous system. The nerve supply does not initiate activity in the muscle but it modifies it by affecting: a) Its spontaneous activity b) Its sensitivity to chemical agents Fig 66: Membrane potentials in intestinal smooth muscle. Note the slow waves, the spike potentials, total depolarization, and hyperpolarization, all of which occur under different physiological conditions of the intestine. Relation of Length to Tension: Plasticity: The smooth muscle is plastic. If it is stretched, it first exerts increased tension. However, if the muscle is maintained stretched, the tension gradually decreases. This property results from readjustment of the position of the myosin cross-bridges on the thin filaments. Due to such a property, urine can accumulate in the urinary bladder without much rise of intravesical pressure. Dr. EL-SHERIF 33