Muscle Physiology PDF

CHAPTER IV: PHYSIOLOGY OF MUSCLE  Learning Objectives At the end of this chapter, students should be able to: Describe types of muscle tissue Explain fine structure of the skeletal muscle State mechanism of muscle contraction Describe the neuromuscular junction...

CHAPTER IV: PHYSIOLOGY OF MUSCLE  Learning Objectives At the end of this chapter, students should be able to: Describe types of muscle tissue Explain fine structure of the skeletal muscle State mechanism of muscle contraction Describe the neuromuscular junction 2  Introduction It is the fleshy organ of the body that converts potential energy of food into mechanical energy. Human body contains over 400 skeletal muscles Accounts 40% of the total BW. Muscle tissue combined with nerves, blood vessels, and various connective tissues is what makes up those muscle organs that are familiar to us. Muscles are quite complex and are a marvel of both biology and physics Functions of muscle: Motion Maintenance of posture Heat production Stabilization of joints  Types of muscles: 3 types (1) 1.Skeletal/voluntary muscles Located attached to bones & moves skeleton They are elongated, cylindrical and multinucleated cells, They are striated muscle They are voluntary muscle, controlled by somatic NS (SNS) 2. Cardiac muscle: Muscle of the heart They are striated, branched and uni/bi-nucleated Cardiac muscle cells are joined by structures called intercalated discs – which consist of desmosomes and gap junctions. They are involuntary, controlled by autonomous NS (ANS), drugs and hormones Have the property of autorhythmicity and syncytium  Types of muscles: 3 types (2) 3. Smooth muscles  Located in the wall of hallow organs (GIT, blood vessels, uterus, urinary bladder, Iris)  They have non-striated appearance, mononucleated cells  involuntary muscle, controlled by ANS, drugs and hormones  Have the property of autorhythmicity and syncytium Types of muscles 6 Classifications 7  Characteristics of Muscle 1. Excitability – The ability to receive and respond to a stimulus In smooth muscle, the stimulus could be a neurotransmitter, a hormone, stretch, pH, Pco2, or Po2. In cardiac muscle, the stimulus could be a neurotransmitter, a hormone, or stretch. In skeletal muscle, the stimulus is a neurotransmitter released by a neuron. – The response is the generation of an electrical impulse that travels along the plasma membrane of the muscle cell. Saturday, February 1, 20 8 25  Characteristics … 2. Contractility – The ability to shorten forcibly when adequately stimulated. – This is the defining property of muscle tissue. 3. Extensibility – The ability to be stretched 4. Elasticity – The ability to recoil and resume original length after being stretched or contracted. Saturday, February 1, 20 9 25  Functions of Muscle 1. Produces Movement – Movement of body parts – Movement of blood throughout the body – Movement of lymph through the lymphatic vessels – Movement of food through the GI tract – Movement of bile out of the gallbladder and into the digestive tract – Movement of urine through the urinary tract – Movement of semen through the male and female reproductive tracts – Movement of a newborn through the birth canal Saturday, February 1, 20 10 25  Functions cont… 2. Maintenance of posture – Muscle contraction is constantly allowing us to remain upright. – The muscles of your neck are keeping your head up right now. – As you stand, your leg muscles keep you on two feet. 3. Thermogenesis – Generation of heat. – Occurs via shivering – an involuntary contraction of skeletal muscle. Saturday, February 1, 20 11 25  Functions cont… 4. Stabilization of joints – Muscles keep the tendons that cross the joint nice and firm. – This does a wonderful job of maintaining the integrity of the joint. Saturday, February 1, 20 12 25  Skeletal Muscle Skeletal muscles are dominated by muscle tissue and also contain nervous, vascular and connective tissues. It surrounded by dense irregular connective tissue known as the epimysium Saturday, February 1, 20 13 25  Skeletal Muscle cont… Epimysium surrounds several bundles known as fascicles. Each fascicle is a bundle of super-long skeletal muscle cells (muscle fibers), surrounded by a layer of dense irregular CT called the perimysium (peri=around). Each muscle cell extends the length of the whole muscle organ and is surrounded by a fine layer of loose connective tissue, the endomysium. Saturday, February 1, 20 14 25  Skeletal Muscle cont… Each skeletal muscle is supplied by  one nerve,  an artery and  one or more veins. They all enter/exit via the connective tissue coverings and branch extensively. Saturday, February 1, 20 15 25  Skeletal Muscle cont… Most joints are attached to bones. – The attachment of the muscle to the immoveable bone in a joint is its origin, while the attachment to the moveable bone is its insertion. Saturday, February 1, 20 16 25  Skeletal Muscle cont… Each skeletal muscle cell is known as a skeletal muscle fiber because they are so long. – Their diameter can be up to 100µm and their length can be as long as 30cm. – They’re so large because a single skeletal muscle cell results from the fusion of hundreds of embryonic precursor cells called myoblasts. A cell made from the fusion of many others is known as a syncytium. Saturday, February 1, 20 17 25 Components of a muscle fiber 18 Fine Structure of the Skeletal Muscle (1) Motor end plate: contact surface with axon terminal Sarcolemma: muscle cell membrane Sarcoplasma: muscle cell cytoplasm – Has lots of mitochondoria – Lots of glycogen granules to provide glucose for energy needs – contains myofibrils, sarcoplasmic reticulum, myoglobin, glycogen and creatin-PK 19  Fine Structure of the Skeletal Muscle (2) Myoglobin It is iron containing protein in muscle cells that gives red coloration to the lean meat Function: to store and reserve oxygen for muscle metabolism A muscle cell has two tubular structures 1. Transverse tubules (T tubules) Function: conduction of depolarisation 2. Longitudinal tubules (sER) Function: Ca2+ storage 20  Fine Structure of the Skeletal Muscle (3) Myofibrils Each muscle fiber contains rod like structures called myofibrils that extend the length of the cell They are basically long bundles of protein structures called myofilaments and their actions give muscle the ability to contract The myofilaments are classified as thick and thin filaments There are also regulatory proteins that form a complex with the thin myofilaments Myofilaments Have 3 components 1. Actin (thin myofilaments) 2. Myosin (thick filaments) 3. Troponin and tropomyosin (regulatory proteins) 21  Myosin structure (The Thick Myofilaments) A single myosin protein resembles 2 golf clubs whose shafts have been twisted about one another About 300 of these myosin molecules are joined together to form a single thick filament The head  forms cross bridges with the thin filaments Presence of the enzyme (ATPase) in the head  release energy for contraction 22 Actin structure (Thin Myofilaments) Formed by 3 different proteins: i. Globular (G) actins: bind to myosin heads ii. Tropomyosin: long, fibrous molecule, extending over actin, and preventing interaction between actin and myosin iii.Troponin: binds reversibly to calcium and able to move tropomyosin away from the actin active site. 23  The myofibrils are organized into a repetitive pattern called the The Sarcomere sarcomere – Myosin: thick filament – Actin: thin filament Bands formed by pattern: – A band: contains only thick filaments (darkened) – I band: contains only thin filaments (Lighted) H zone: contains only thick filaments Z line: area of attachment of the actin fibers M line: Myosin fiber centers A stands for Anisotropic I stands for Isotropic 24  T-Tubules and the SR Each muscle fiber has many T-tubules Typically each myofibril has a branch of a T-tubule encircling it at each A-I junction At each A-I junction, the SR will expand and form a dilated disc (terminal cisterna) Each T-tubule will be flanked by a terminal cisterna This forms a so called triad consisting of two terminal cisternae and one T-tubule branch 25  Muscle contraction: The Sliding Filament Hypothesis Hanson and Haxley – Proposed that the skeletal muscles shorten during contraction because the thick and the thin myofilaments slide past one another – Their model is known as the sliding filament mechanism of muscle contraction – The thin filaments slide over the thick filaments – This pulls the Z discs closer together – When all the sarcomeres in a fiber do this; The entire fiber gets shorter which pulls the endomysium, perimysium and epimysium come together to form tendon attached to the bone. The sarcomere and the muscle fibers shortens. 26 Muscle contraction (The Sliding Filament Hypothesis) The sliding filament model – Muscle shortening occurs due to the movement of the actin filament over the myosin filament – Formation of cross-bridges between actin and myosin filaments – Reduction in the distance between Z-lines of the sarcomere 27  Muscle contraction… We can actually divide the whole process of muscle contraction into 4 steps: – Excitation – Excitation-contraction coupling – Contraction – Relaxation Saturday, February 1, 20 25  Excitation All cells have a voltage difference across their plasma membrane. This is the result of several things: 1. The ECF is very high in Na+ while the ICF is very high in K+. - The PM is impermeable to Na+ but slightly permeable to K+. As a result, K+ is constantly leaking out of the cell; In other words, positive charge is constantly leaking out of the cell. Saturday, February 1, 20 29 25  Excitation cont… 2.The Na+/K+ pump is constantly pumping 3 Na+ ions out and 2 K+ ions in for every ATP used. Thus more positive charge is leaving than entering. 3. There are protein anions (i.e., negatively charged proteins) within the ICF that cannot travel through the PM. What this adds up to is the fact that the inside of the cell is negative with respect to the outside. The interior has less positive charge than the exterior. This charge separation is known as a membrane potential (abbreviated Vm). The value for Vm in inactive muscle cells is typically btwn –80 and –90 millivolts. Saturday, February 1, 20 30 25  Excitation cont… Cells that exhibit a Vm are said to be polarized. Vm can be changed by influx or efflux of charge. The PM has integral proteins that act as gated ion channels. These are channels that are normally closed, but in response to a certain signal, they will open and allow specific ions to pass through them. Saturday, February 1, 20 31 25  Excitation cont… Ion channels may be: – Ligand-gated  the binding of an extracellular molecule (e.g., hormone, neurotransmitter) causes these channels to open. – Voltage-gated  Vm causes these channels to open. – Mechanically-gated  stretch or mechanical pressure opens these channels. When a channel is open, its specific ion(s) will enter or exit depending on their electrochemical gradient. In general each muscle is served by one nerve – a bundle of axons carrying signals from the spinal cord to the muscle. Saturday, February 1, 20 32 25  Excitation cont… Each muscle is served by one nerve – A bundle of axons carrying signals from the spinal cord to the muscle With in the muscle, each axon will go its own way and eventually branch into multiple small extensions called telodendria Each telodendrium ends in a bulbous swelling known as the synaptic end bulb The site of interaction b/n a neuron and any other cell is known as a synapse. The synapse b/n a neuron and a muscle is known as the neuromuscular junction (NMJ). A motor unit: is defined as a somatic motor neuron and all the skeletal muscle fibers it innervates. 33  The Neuromuscular Junction The minute space between the synaptic end bulb and the sarcolemma is known as the synaptic cleft. There is a depression in the sarcolemma at the synaptic cleft known as the motor end plate. The synaptic end bulb is filled w/ vesicles that contain the neurotransmitter, acetylcholine. The motor end plate is chock full of acetylcholine receptors, nicotinic receptor. 34 Transmission of Nerve Impulse at the NMJ (1) 1. A nerve signal will arrive at the synaptic end bulb and this will cause the ACh-containing vesicles to undergo exocytosis. 2. ACh will diffuse across the synaptic cleft and bind to the ACh receptors. These receptors are actually ligand-gated Na+ channels. The binding of ACh causes them to open. 3. Na+ will rush into the cell, making the local cell interior more positive. This is known as depolarization. It is a local event! 35 Transmission of Nerve Impulse at the NMJ (2) 4. Adjacent to the motor end plate, the sarcolemma contains voltage-gated ion channels. In order for these channels to open, the membrane must depolarize from its resting value of -9omv to approximately -50mv. This is the threshold 5. The degree of depolarization depends on how much Na+ influx occurs which in turn depends on how many Na+ channels were opened by binding Ach. 6. If the membrane fails to depolarize to threshold, nothing will happen. 36 Synaptic events 37  Characteristics of neuromuscular junction Transmission is unidirectional There is a single NMJ per muscle fiber The neurotransmitter is always acetylcholine (Ach) Synthesis: Choline + Acetyl-COA = ACh by the action of choline acetyl-COA transferase Storage: Ach form a complex with ATP, packed in vesicles Release: Released by Ca-dependent exocytosis Metabolism: Metabolized by the action of ACh-Esterase The post junctional receptor is always nicotinic receptor The effect of Ach on NR is always excitatory producing EPSP/end plate potential (EPP) EPP has high safety margin There is a synaptic delay (0.2 – 03 ms) It is fatigable due to depletion of ATP and NT storage 38  Factors affecting the NMJ  Can be affected by various factors – Calcium level: Hypercalcimia inhibits membrane excitability Hypocalcimia increases membrane excitability – Hypoxia: inhibits membrane excitability – Drugs: 1. Ach- release inhibitors: Botulin toxin extracted from Clostridium botulinum 2. Nicotinic receptor (cholinergic) blockers: d-tubocurarine, α-cobratoxin 3. Cholinergic stimulants: nicotine, metacholine, carbacholine 4. Anti-cholinstrase drugs: Physiostegmin, neostegmin and Diisopropylfluorophosphate (DFP) 39  Excitation-contraction coupling (1) When a muscle fibre membrane is depolarized, contraction of the fibre follows. The process by which depolarization initiates contraction is called excitation contraction coupling. It has several steps as follow: 1. Action potential initiated & propagated along the motor nerve fibre and arrives at the end feet. 2. Opening of VG-Ca-channels and influx of Ca2+ to trigger the release of Ach. 3. Ach released by Ca-dependent exocytosis and diffuse through the synaptic cleft and binds to NR on post-junctional membrane. 4. Opening of ligand gated Na-channels and influx of Na+ to produce EPP. 5. Spread of depolarization through the sarcolemma 6. Spread of depolarization through the T-tubules 40  Excitation-contraction coupling (2) 7. Depolarization of T-tubules stimulate SR to release Ca2+ into sarcoplasm 8. Ca2+ binds to troponin-C 9. Ca2+ and troponin-C combination detaches troponin-I from the active sites of actin 10. The detachment of troponin-I from actin displaces tropomyocin, uncovering the active sites of actin filaments. 11. When the active site of actin exposed, the heads of myosin connect to them, making cross-bridges b/n myosin and actin. 12. The ATPase enzyme on the myosin heads hydrolyze ATP into ADP + -P plus energy. 13. The released energy causes the movt of the head (power stroke) towards the centre. 14. The head of myosin is charged with a new molecule of ATP and then detached from actin leading to relaxation. 41  Mechanism of muscle relaxation  It has the following steps 1. Following muscle contraction, Ca2+ is re-uptaken back into SR by Ca-pump, this requires ATP. 2. Decreased Ca2+ in the sarcoplasm→ Ca2+ detaches from troponin-C →Tropomyosin covers the active sites of actin. 3. Head of myosin charged with ATP, and detached from actin  Therefore, muscle relaxation is an active process requiring energy.  Large amount of energy (ATP) is consumed during muscular performance for the following activities: 1. To move the head of myosin (power stroke) 2. Active Ca2+ pump from sarcoplasm to SR 3. For Na-K-pump in the membrane 4. For muscle relaxation 42  Types of Skeletal Muscle Fibers Based on the velocity of shortening, major pathways used to form ATP and fatigability, muscle fibers are classified into 2 types as 1. Slow fibers 2. Fast fibers Slow fibers  Contract slowly because its myosin ATPases work slowly.  Depends on oxygen delivery and aerobic metabolism  Is fatigue resistant and has high endurance.  Is thin in diameter – large amount of cytoplasm impedes O2 and nutrient diffusion. 43  Slow Fibers Cont’d… Cannot develop high tension – small diameter means few myofibrils. Has rich capillary supply and lots of mitochondria. Contains lots of the O2-storing protein, myoglobin which gives it a red color. Uses lipids, CHO, and amino acids as substrates for its aerobic metabolism. Best suited for endurance type activities. Red fibers, slow oxidative fibers, type I fibers. 44  Fast Fibers So named because they can contract in 0.01 seconds or less after stimulation. Fast fibers are large in diameter; they contain densely packed myofibrils, large glycogen reserves, and relatively few mitochondria. Able to develop a great deal of tension b/c they contain a large number of sarcomeres. Use ATP in massive amounts. Supported by anaerobic metabolism. Fatigue rapidly. fast fatigue (FF) fibers, fast glycolytic (FG) fibers, white fibers. Best suited for short term, power activities. 45  Myasthenia Gravis (1) My=muscle, asthen=weakness, gravi=heavy It is the defect in the NMJ, characterized by easy fatigability of the skeletal muscle. Results in progressive weakening of the skeletal muscles. Possible causes Autoimmune disease where antibodies attack the NR on neuromuscular junctions. High thymopoietin is another Decrease in quantity of Ach release Decrease in number of NR on neuromuscular junctions Decrease in post-junctional folds Increase in width of synaptic cleft 46  Myasthenia Gravis (2) Treatment: Anticholinesterase: anticholinesterases such as neostigmine or physostigmine. – These decrease the activity of acteylcholinesterase. Steriods, which are immunosuppressants 47  Smooth Muscle Smooth muscle is always maintaining a normal level of activity which creating muscle tone Can respond to stimuli by altering this tone in either direction – Smooth muscle can be inhibited and relax – Smooth muscle can be excited and contract Possible stimuli include NTs, hormones, ∆pH, ∆PCO2, ∆PO2, metabolites (such as lactic acid, ADP) or even stretch 48  Contraction of smooth muscle Smooth muscle contains both actin and myosin filaments Does not contain the troponin complex The contractile process is activated by Ca2+ and ATP is degraded to ADP to provide the energy for contraction Calcium ions combine with calmodulin to cause activation of myosin kinase and phosphorylation of the myosin head→ binds to actin→ contraction 49 50 51  Cardiac muscle contraction 1. Ca2+- release from the SR is triggered by Ca2+ (not by sodium depolarization 2. T-Tubule contains Ca2+ channel through which Ca2+ enters the cell during the AP). 3. This Ca++ triggers release of Ca++ from SR 4. Ca++ binds to Troponin C 5. Ca++-Troponin complex interacts with tropomyosin (to unlock active site between actin and myosin) 6. Cross bridge cycling = contraction (systole) 52 53