Muscle Physiology 2024 PDF

Physiology of Muscle Prof. A. Danborno Department of Physiology, Faculty of Basic Medical Sciences, Bingham University, Karu  Types of Muscle Skeletal Attached to bones Makes up 40% of body weight Responsible for l...

Physiology of Muscle Prof. A. Danborno Department of Physiology, Faculty of Basic Medical Sciences, Bingham University, Karu  Types of Muscle Skeletal Attached to bones Makes up 40% of body weight Responsible for locomotion, facial expressions, posture, respiratory movements, other types of body movement Voluntary in action; controlled by somatic motor neurons Smooth In the walls of hollow organs, blood vessels, eye, glands, uterus, skin Some functions: propel urine, mix food in digestive tract, dilating/constricting pupils, regulating blood flow, In some locations, auto rhythmic Controlled involuntarily by endocrine and autonomic nervous systems Cardiac Heart: major source of movement of blood Auto rhythmic Controlled involuntarily by endocrine and autonomic nervous systems  Skeletal muscle functions Produce skeletal movement Maintain posture and body position Support soft tissues Guard entrances and exits Maintain body temperature  Layers of Skeletal Muscle Connective Tissue of a Muscle Epimysium. Dense regular c.t. surrounding entire muscle Separates muscle from surrounding tissues and organs Perimysium. Collagen and elastic fibers surrounding a group of muscle fibers called a fascicle Contains blood vessels and nerves Endomysium. Loose connective tissue that surrounds individual muscle fibers Also contains blood vessels, nerves, and satellite cells Sarcomere Structure Sarcomere: functional unit of striated muscle Levels of Functional Organization in Skeletal Muscle Fiber  Muscle Terminology Muscle fiber (muscle cell) Sarcolemma (cell membrane) Sarcoplasm (muscle cell cytoplasm) Sarcoplasmic reticulum (modified ER) T-tubules and myofibrils aid in contraction Sarcomeres – regular arrangement of myofibrils Sarcoplasmic Reticulum (SR) SR is an elaborate, smooth endoplasmic reticulum runs longitudinally and surrounds each myofibril SR stores Ca++ when muscle is not contracting When stimulated, calcium released into sarcoplasm SR membrane has Ca++ pumps that function to pump Ca++ out of the sarcoplasm back into the SR after contraction Myosin Many elongated myosin molecules shaped like golf clubs. (Thick) Single filament contains roughly Myofilament 300 myosin molecules Molecule consists of two heavy myosin molecules wound together to form a rod portion lying parallel to the myosin myofilament and two heads that extend laterally. Myosin heads 1. Each myosin heads has 2 binding sites on it: one for an ATP molecule and one for actin 2. Have ATPase activity: activity that breaks down adenosine triphosphate (ATP), releasing energy. Part of the energy is used to bend the hinge region of the myosin molecule during contraction  Thin Filament: composed of 3 major proteins Actin (Thin) 1. F (fibrous) actin Myofilaments 2. Tropomyosin 3. Troponin Two strands of fibrous (F) actin form a double helix extending the length of the myofilament; attached at either end at sarcomere. Composed of G actin monomers each of which has a myosin- binding site (see yellow dot) Actin site can bind myosin during muscle contraction. Tropomyosin: an elongated protein winds along the groove of the F actin double helix. Troponin is composed of three subunits: Tn-A : binds to actin Tn-T :binds to tropomyosin, Tn-C :binds to calcium ions. Actin filament  Sliding filament theory Explains the relationship between thick and thin filaments as contraction proceeds Cyclic process beginning with calcium release from SR Calcium binds to troponin Troponin moves, moving tropomyosin and exposing actin active site Myosin head forms cross bridge and bends toward H zone ATP allows release of cross bridge  Sliding Filament Model of Contraction Thin filaments slide past the thick ones so that the actin and myosin filaments overlap to a greater degree In the relaxed state, thin and thick filaments overlap only slightly Upon stimulation, myosin heads bind to actin and sliding begins Changes in the appearance of a Sarcomere during the Contraction of a Skeletal Muscle Fiber Sarcomere Relaxed Sarcomere Partially Contracted Sarcomere Completely Contracted  Neuromuscular Junction The neuromuscular junction is a synaptic connection between the terminal end of a motor nerve and a muscle. It is the site for the transmission of action potential from nerve to the muscle. The structure of NMJ can be divided into three main parts: a presynaptic part (nerve terminal), the postsynaptic part (motor endplate), and an area between the nerve terminal and muscle (synaptic cleft). Motor Neuron  Neuromuscular Transmission A nerve terminal contains mitochondria, endoplasmic reticulum, and synaptic vesicles Each synaptic vessicles stores around 5000- 10000 molecules of acetylcholine (ACh), the neurotransmitter at neuromuscular junction. On arrival of an action potential at the nerve terminal, Ca channels open to cause influx. Neuromuscular Transmission… Increased Ca inside the nerve terminal causes a series of events leading to docking of synaptic vesicles and exocytosis of the ACh from the synaptic vesicles into the synaptic cleft. The space between the nerve terminal and the plasma membrane of muscle is called synaptic/junctional cleft and measures ∼50 nm. Neuromuscular Transmission… It is the site where presynaptic neurotransmitters, ACh is released. Synaptic cleft of neuromuscular junction contains acetylcholinesterase enzyme, responsible for the break down of released ACh so that its effect on the post-synaptic receptors is not prolonged. Neuromuscular Transmission… Motor End Plate forms the postsynaptic part of neuromuscular junction. It is the thickened portion of the muscle plasma membrane (sarcolemma) that is folded to form depressions called junctional folds. Junctional folds have nicotinic ACh receptors concentrated at the top. Neuromuscular Transmission Binding of ACh to these receptors opens the channels allowing the influx of sodium ions from the extracellular fluid into the muscle membrane. This creates endplate potential and generates and transmits AP to the muscle membrane Acetylcholine Opens Na+ Channel  Acetylcholine synthesis In the cholinergic neurons acetylcholine is synthesized from choline. This reaction is activated by cholineacetyltransferase As soon as acetylcholine is synthesized, it is stored within the synaptic vesicles. 52  Removal of Acetylcholine from the synaptic cleft: In order to ready the synapse for another impulse: 1) The neurotransmitters, which are released from the synaptic vesicles, are hydrolyzed by enzyme present in the synaptic cleft “Acetylcholinestrase” giving choline, which poorly binds to acetylcholine receptors. Acetylcholine + H2O Choline + H+ Acetylcholinestrase acetate 2) The empty synaptic vesicles, which are returned to the axonal terminal bulb by endocytosis, must be filled with acetylcholine. 53  Synaptic events The AP reaches the axonal bulb Voltage-gated calcium channels open The influx of calcium in the bulb activates enzymes the vesicles containing the neurotransmitter molecule dock and release the neurotransmitter in the synapse The neurotransmitter for skeletal muscles is always acetylcholine The receptors on the muscle fiber are cholinergic receptors These receptors are nicotinic (fast) acting receptors Excitation Contraction Coupling Nerve impulse reaches myoneural junction Acetylcholine is released from motor neuron Ach binds with receptors in the muscle membrane to allow sodium to enter Sodium influx will generate an action potential in the sarcolemma Action potential travels down T tubule Excitation Contraction Coupling… Sarcoplasmic reticulum releases calcium Calcium binds with troponin to move the troponin, tropomyosin complex Binding sites in the actin filament are exposed Myosin head attach to binding sites and create a power stroke ATP detaches myosin heads and energizes them for another contraction When action potentials cease the muscle stop contracting  Muscle relaxation Ach is removed from the receptors by acetylcholinesterase Na+ channels close Na/K pumps reestablish the RMP Ca++ ions leave troponin and are brought back into the SR (this process needs energy) Tropomyosin moves back over the actin active site The myosin heads release their binding to actin The filaments passively move back into resting position  Myasthenia Gravis It is an autoimmune disease where the immune system of affected individuals generates antibodies against the bodies own nicotinic ACh receptors. The antibodies bind to the receptors, and destroy them, thereby interfering with the normal actions of ACh at the neuromuscular junction. This destruction leaves the muscle with fewer Ach receptors in the membrane. So even though neurotransmitter release is normal, the muscle target has a diminished response that is exhibited as muscle weakness.  Myasthenia Gravis So a muscle action potential does not result from a nerve impulse, and so the muscle fail to contract. The disease is characterized by muscular weakness and extreme fatigue of voluntary muscle. These patients can be managed with IV immunoglobulins, which bind up the auto-antibodies, or plasmapheresis, which remove the autoantibodies from the blood. Patients with a respiratory crisis may also require ventilatory support  Lambert-Eaton syndrome It is a rare, autoimmune disorder in which the body's immune system attacks the connections between nerves and muscles. It is most often seen in people with small cell lung cancer or other cancers, but it can also occur in people without cancer. The individuals generate antibodies against voltage-gated calcium channels on the pre- synaptic membrane. Lambert-Eaton syndrome… This prevents Ca from entering the nerve terminal and triggering the fusion of ACh vesicles with the synaptic membrane. Therefore, it essentially prevents the release of ACh into the synaptic cleft and ultimately prevents muscle contraction.  Contractions Isometric Contraction: Isotonic Contraction: Tension rises, length of Tension rises, length of muscle remains constant muscle changes Produces no Produces movement movement Used in Used in Walking Standing Moving any part of Sitting the body Posture  Events during the twitch Twitch is a cycle of contraction, relaxation produced by a single stimulus. Latent phase: Stimulus to beginning contraction: AP to myosin binding to actin active site Contraction phase: beginning to end of muscle tension  myosin heads slide along the actin filaments Relaxation phase: peak tension to no tension  Ca++ ions moved back into the cisternae, tropomyosin moves back over actin, myosin head release actin and the filaments move back into resting position Contraction Speed  Summation Repeated stimulation before relaxation phase has been completed Wave summation = one twitch is added to another Incomplete tetanus = muscle never relaxes completely Complete tetanus = relaxation phase is eliminated Energy use and Muscle Contraction Muscle Contraction requires large amounts of energy. Creatine phosphate releases stored energy for muscle contraction. Aerobic metabolism provides most ATP needed for contraction. At peak activity, anaerobic glycolysis needed to generate ATP. Muscle metabolism Muscle fibers use ATP (only first few seconds) for contraction ATP must then be generated by the muscle cell: - from creatine phosphate, first - from glucose and glycogen - from fatty-acids ATP formation from the above compound is possible if oxygen is present (oxidative phosphorylation: 36 ATP per glucose) Oxygen is delivered to the muscle by myoglobin, a molecule with high affinity to oxygen and related to hemoglobin  Muscle metabolism If the effort is strong and sustained, the muscle might not have enough oxygen delivered to it by myoglobin  anaerobic glycolysis with only 2 ATP formed per glucose and synthesis of lactic acid Consequence of anaerobic metabolism?  Muscle fatigue Muscle fatigue: a decline in the ability of the muscle to sustain the strength of contraction Causes: - rapid build-up of lactic acid - decrease in oxygen supply - decrease in energy supply (glucose, glycogen, fatty- acids) - Decreased neurotransmitter at the synapse  Muscle Fatigue… Fatigue is often defined as an overwhelming sense of tiredness, lack of energy and feeling of exhaustion, fatigue relates to a difficulty in performing voluntary tasks (Gruet et al, 2013) Fatigue accumulation, if not resolved, leads to overwork, chronic fatigue syndrome (CFS). over-training syndrome, and even endocrine disorders, immunity dysfunction, organic diseases and a threat to human health (Jing- jing Wan et al., 2017).  Muscle Performance Types of skeletal muscle fibers Skeletal muscle fibers can be classified according to their speed of contraction and resistance to fatigue into two: 1) Slow fibers 2) Fast fibers Skeletal Muscle Fiber Types generally categorized by histochemical criteria into: Slow twitch fibers: Type I Fast twitch fibers type: Type II pumps calcium into their SR more rapidly. Type II can further be divided into type IIa and Type IIb So fast twitch fibers have quicker twitches. Skeletal Muscle Fiber Types… all human muscles contain mixture of three general fiber types slow twitch (oxidative, red, Type I) rely on oxidative phosphorylation to produce ATP. fast twitch (fast oxidative-glycolytic, white, Type IIa) fast twitch (fast glycolytic, white, Type IIb) depend on anaerobic glycolysis to produce ATP  Types of Skeletal Muscle Fibers… People are genetically predisposed to have relatively more of one fiber type than another People who excel at marathon running have higher percentages of slow twitch fatigue resistant muscle fibers People who excel at sprinting have higher percentages of fast twitch fatigable fibers  Effects of exercise on the muscle Aerobic exercises: long sustained exercises  Endurance promote increased oxidative capacity of the muscle fiber  increased blood vessel supply, increased mitochondria High intensity, short burst exercise: increased glycolytic activity  increased synthesis of glycolytic enzymes, increased synthesis of myofibrils (increased muscle size)  Performance Declines with Aging --despite maintenance of physical activity  Smooth Muscle Although skeletal muscle has the most muscle mass in the body, cardiac and smooth muscle are more important in the maintenance of homeostasis. Smooth muscle is found predominantly in the walls of hollow organs and tubes, where its contraction changes the shape of the organ. Smooth muscle usually generates force to move material through the lumen of the organ  Smooth Muscle Smooth muscle has low oxygen consumption rates, yet it can sustain contractions for extended periods without fatiguing. This property allows organs such as the bladder to maintain tension despite a continued load.  Smooth Muscle… In comparison to skeletal muscle fibers Smooth muscle fibers are shorter and thinner They have a single, centrally located nucleus Lack striations Although smooth muscle fibers contain actin and myosin, the filaments are thin and randomly arranged so that it lacks striations No T-tubules A poorly developed sarcoplasmic reticulum  Smooth Muscle… Autonomic nervous system control Unconscious control of smooth muscle contraction Neurotransmitters Acetylcholine (as in skeletal muscle) Noradrenaline. Neurotransmitters for smooth muscle can be either excitatory (cause muscle contraction), or inhibitory (prevent muscle contraction) depending on the receptor on the smooth muscle cell membrane. Whereas, the neurotransmitter for skeletal muscle is always excitatory. Smooth muscle is also stimulated by certain hormones such as oxytocin, which stimulates smooth muscle contraction in the walls of the uterus during childbirth. Types of Smooth Muscle Visceral or unitary smooth muscle Only a few muscle fibers are innervated in each group Impulse spreads through gap junctions Their sheet contracts as a unit Often auto rhythmic Multiunit: Cells or groups of cells act as independent units Piloerector of the skin and iris of eye Multiunit smooth muscle Fibers are not very well organized Occur as separate fibers scattered throughout the sarcoplasm rather than in sheets. Requires stimulation by a motor nerve impulse from the autonomic nervous system. This type of smooth muscle is found in the irises of the eyes, erector pili muscles, blood vessels, and large airways of the lungs Multi-Unit Muscle  Single Unit Smooth Muscle Also called Visceral Smooth Muscle because it is found in the walls of the hollow visceral organs such as the stomach, intestines, urinary bladder and uterus. More common of the two types of smooth muscle. The muscle fibers are organized into sheets of cells held in close contact by gap junctions. Organized into two layers: Longitudinal layer Outer layer directed longitudinally along the length of the structure. Contraction of this layer causes the structure to dilate and shorten Circular layer Inner layer arranged circularly around the structure. Contraction of this layer causes the structure to constrict and elongate. Single-Unit Muscle Multi vs. Single-Unit Muscle  Smooth Muscle contraction Smooth muscle fibers contract in a similar manner to skeletal muscles with a few important functional similarities and differences. Similarities Both contractile mechanisms depend on the action of actin and myosin; Both are triggered by membrane impulses and the release of calcium ions; and Both require ATP. Smooth Muscle contraction Differences in smooth muscle include Actin has no troponin, the protein that binds to calcium in skeletal muscle. Rather smooth muscle has a calcium binding protein called calmodulin. This protein activates the actin and myosin crossbridge formation. Most of the calcium required for contraction comes into the cell by diffusion from the extracellular fluid. Smooth muscle is more resistant to fatigue and produces a slower, longer lasting contraction than skeletal muscle. It is more energy efficient than skeletal muscle in that it can maintain a more forceful contraction for a longer period of time with the same amount of ATP. Smooth Muscle Contraction: Mechanism Smooth Muscle Relaxation: Mechanism Intrinsic Control of Smooth Muscle Contraction Myogenic Response Smooth muscle is stimulated to contract when it is stretched Smooth muscle is able to distend, or stretch, without great increases in tension or tightness Allows hollow organs to be filled When the smooth muscle reaches its stretching capacity, it will contract and force the contents out Such as occurs in the intestines or urinary bladder.  Cardiac Muscle Found only in the heart Composed of interconnecting, branching fibers that are striated Each cell has a single nucleus Contains actin and myosin similar to smooth muscle. Abundant mitochondria Depends on aerobic metabolism It cannot sustain an oxygen debt and still function efficiently  Cardiac Muscle Highly coordinated contractions of cardiac muscle pump blood into the vessels of the circulatory system. Similar to skeletal muscle, cardiac muscle is striated and organized into sarcomeres, possessing the same banding organization as skeletal muscle However, cardiac muscle fibers are shorter than skeletal muscle fibers and usually contain only one nucleus, which is located in the central region of the cell. Cardiac muscle fibers also possess many mitochondria and myoglobin, as ATP is produced primarily through aerobic metabolism Disamba, 9 2024 106 Cardiac Muscle Tissue Figure 10.10a  Cardiac Muscle Under control of the ANS (involuntary) and endocrine system (hormones) Some cells are autorhythmic Fibers spontaneously contract (aka Pacemaker cells) Contains intercalated disks Membrane junctions that hold adjacent cells together and transmit the contraction force to each cell Allow excitation in one fiber to spread quickly to adjoining fibers  Cardiac Muscle... Extensive system of T-tubules Release large quantities of calcium ions Well developed sarcoplasmic reticulum Strength of the cardiac muscle contraction depends largely on the influx of calcium from the extracellular space in addition to that released from the T-tubules and sarcoplasmic reticulum Gap Junctions Most important intercellular junction that allow interchange and communication between the sarcoplasm of connected cardiac muscle cells  Cardiac Muscle Contraction Cardiac muscle, like skeletal muscle and neurons, is an excitable tissue with the ability to generate action potentials. But in cardiac muscle cells, calcium plays a very important role in the action potential. In addition to the depolarization phase, there is a plateau phase in cardiac muscle which is brought about by the influx of calcium from the extracellular fluid.  Cardiac Muscle Contraction… Plateau Phase The prolonged depolarization in cardiac muscle due to Calcium influx from the extra-cellular fluid The prolonged plateau phase prevents prolonged contractions, that would interfere with the pumping ability of the heart Refractory Period Due to the calcium influx in cardiac muscle, there is a prolonged absolute refractory period of cardiac muscle lasting about 250 msec. Much longer than skeletal muscle which lasts about 1-2 msec. Repolarization Calcium is pumped back into sarcoplasmic reticulum and out of cell to the extracellular space.  Cardiac Muscle… Cardiac muscle is self-exciting It is able to stimulate itself to contract Cardiac muscle is autorhythmic It contracts in a periodic manner Autorhythmicity causes the automatic contraction and relaxation of the heart Known as the heartbeat.  Cardiac Muscle… Autorhythmicity Ability of cardiac muscle to repeatedly and rhythmically contract without external stimulation Due to the presence of Pacemaker Cells in the heart Specialized cardiac muscle cells that depolarize spontaneously at regular intervals causing excitation of the muscle cells without nervous system stimulation The spontaneous impulses travel into the surrounding muscle tissue through gap junctions that connect the cell membranes of adjacent muscle fibers, thus allowing the heart to contract as a coordinated unit. Comparisons Among Skeletal, Smooth, and Cardiac Muscle