FTM 35 Muscle (1) PDF

Basic Principles of Medicine 1 Module: Foundation to Medicine Lecture No: 35 Muscle Tissue Dr Davina C M Simoes MSc PhD FHEA Assistant Professor in Cellular Pathology, Dept. Applied Sciences, Faculty of Health and Life Sciences davina.simoes@...

Basic Principles of Medicine 1 Module: Foundation to Medicine Lecture No: 35 Muscle Tissue Dr Davina C M Simoes MSc PhD FHEA Assistant Professor in Cellular Pathology, Dept. Applied Sciences, Faculty of Health and Life Sciences [email protected] Session ID: davina1 Copyright All year 1 courses materials, whether in print or online, are protected by copyright. The work, or parts of it, may not be copied, distributed or published in any form, printed, electronic or otherwise. As an exception, students enrolled in year 1 of St. George’s University School of Medicine and their faculty are permitted to make electronic or print copies of all downloadable files for personal and classroom use only, provided that no alterations to the documents are made and that the copyright statement is maintained in all copies. View only files, such as lecture recordings, are explicitly excluded from download and creating copies of these recordings by students and other users are strictly illegal. The author of this document has made the best effort to observe current copyright law and the copyright policy of St George's University. Users of this document identifying potential violations of these regulations are asked to bring their concern to the attention of the author. Session ID: davina1  Assigned Reading Histology – A Text and Atlas Pawlina 8th Edition Chapter 11: Muscle Tissue Pg. 336-379 https://periodicals.sgu.edu/login?url=https://meded-lwwhealthlibrary- com.periodicals.sgu.edu/book.aspx?bookid=2583 Session ID: davina1  Objectives SOM.MK.I.BPM1.1.FTM.3.HCB.0179 Describe the functions of muscle tissue. SOM.MK.I.BPM1.1.FTM.3.HCB.0180 Describe the structure of thick filaments. SOM.MK.I.BPM1.1.FTM.3.HCB.0181 Describe the structure of thin filaments. SOM.MK.I.BPM1.1.FTM.3.HCB.0182 Describe the structure and function of the associated proteins of thick myofilaments. SOM.MK.I.BPM1.1.FTM.3.HCB.0183 Describe the structure and function of the associated proteins of thin myofilaments. SOM.MK.I.BPM1.1.FTM.3.HCB.0184 Give the function of the sarcomere. SOM.MK.I.BPM1.1.FTM.3.HCB.0185 Describe the structure of the sarcomere. SOM.MK.I.BPM1.1.FTM.3.HCB.0186 List the 2 types of striated muscle. SOM.MK.I.BPM1.1.FTM.3.HCB.0187 Describe the contractile apparatus of striated muscle fibers. SOM.MK.I.BPM1.1.FTM.3.HCB.0188 State the functions of the accessory proteins associated striated muscle cells. SOM.MK.I.BPM1.1.FTM.3.HCB.0189 State the function(s) of the accessory proteins associated smooth muscle cells. Describe the general organization of skeletal muscle including connective tissue, SOM.MK.I.BPM1.1.FTM.3.HCB.0190 muscle fascicles, muscle fibers, myofibrils and myofilaments. Describe the structure, function and localization of the T-tubules and the sarcoplasmic SOM.MK.I.BPM1.1.FTM.3.HCB.0191 reticulum in skeletal muscle. BPM1 | FTM | Lecture 35 | Muscle Tissue Describe the general organization of cardiac muscle, including the structure and SOM.MK.I.BPM1.1.FTM.3.HCB.0192 function of intercalated discs and Purkinje fibers. Describe the structure, function and localization of the T-tubules and the sarcoplasmic SOM.MK.I.BPM1.1.FTM.3.HCB.0193 reticulum in cardiac muscle. SOM.MK.I.BPM1.1.FTM.3.HCB.0194 Describe the contractile apparatus of smooth muscle cells. SOM.MK.I.BPM1.1.FTM.3.HCB.0195 Describe the three types of skeletal muscle fibers. SOM.MK.I.BPM1.1.FTM.3.HCB.0196 Describe the regenerative capability of skeletal, cardiac & smooth muscle. SOM.MK.I.BPM1.1.FTM.3.HCB.0197 Describe the sliding filament model of muscle contraction. SOM.MK.I.BPM1.1.FTM.3.HCB.0198 Describe brief ly the events of the actomyosin cross-bridge cycle. SOM.MK.I.BPM1.1.FTM.3.HCB.0199 Describe the structure, function, and localization of skeletal muscle. Describe the ultrastructural defects in muscular dystrophies including Duchenne SOM.MK.I.BPM1.1.FTM.3.HCB.0200 muscular dystrophy.  Objectives SOM.MK.I.BPM1.1.FTM.3.HCB.0201 Give the function of the muscle spindle. SOM.MK.I.BPM1.1.FTM.3.HCB.0202 Give the function of the Golgi tendon organs. SOM.MK.I.BPM1.1.FTM.3.HCB.0203 Describe the histological structure of the muscle spindle. SOM.MK.I.BPM1.1.FTM.3.HCB.0204 Describe the histological structure of the Golgi tendon organs. SOM.MK.I.BPM1.1.FTM.3.HCB.0205 Describe the structure, function, and localization of cardiac muscle. SOM.MK.I.BPM1.1.FTM.3.HCB.0206 Describe the structure, function, and localization of smooth muscle. BPM1 | FTM | Lecture 35 | Muscle Tissue  Primary Tissue Muscle tissue Epithelium Connective tissue Nerve tissue Session ID: davina1  SOM.MK.I.BPM1.1.FTM.3.HCB.0049//0050 Tissue Overview Tissue - the organization of individual cells into groups to perform a specific function(s) 4 Basic Tissue Types 1. Epithelial tissue - Covers body surfaces, lines body cavities, and forms glands - Originates from all 3 germ cell layers a. Ectoderm- e.g., epidermis (skin), epithelium of- oral cavity, eyes, ears b. Mesoderm – epithelium of blood vessels (endothelium) and lining of internal cavities (mesothelium) (e.g., peritoneal, pleural cavities) Ectoderm c. Endoderm – e.g., epithelium lining respiratory system, digestive tract, liver, gallbladder, pancreas, thyroid, parathyroid glands 2. Connective tissue (CT) - Underlies or supports the other three basic Mesoderm tissues structurally & functionally - Embryonic CT derived from mesodermal germ cell layer Endoderm 3. Muscle tissue - Consists of contractile cells and responsible for movement - Derived from the mesoderm 4. Nerve tissue - Receives, transmits and integrates information from outside & inside the body to control activities of the body - Mainly originates from the Myocytes (cells) are referred to as myofibers What is the function of muscles ? Session ID: davina1 Lecture Outline Learning general terms Morphological classification A. Skeletal muscle 1. Muscle histogenesis 2. Tissue organisation 3. Types of skeletal muscle cells 4. Histological structures 5. Myofilaments and accessory proteins 6. Clinical correlation 7. Regulation of muscle contraction 8. Motor Innervation – Neuromuscular Junction 9. Clinical correlation 10. Sensory innervation B. Cardiac muscle C. Smooth muscle Session ID: davina1  General terms Muscle tissue is a specialized tissue for contraction producing movement of the body and changing in volume and shape of internal organs Terms usually associated with muscle tissue – Myo→ myocyte = muscle cell = myofiber – Sarco = Gr. flesh → sarcoplasm (cytoplasm), sarcolemma (plasma membrane), sarcoplasmic reticulum (endoplasmic reticulum) – Skeletal muscle cell = myocyte = myofiber Myofibrils are contractile organelles in the myocyte Myofilaments are the contractile elements in the myofibril The arrangement of myofilaments allows for morphological classification based on the appearance under light microscope Myocyte > Myofibril > Myofilaments SOM.1ai.BPM1.1.FTM.3.HCB.0165 Session ID: davina1  Morphological classification Classification Striated muscle. Smooth muscle. (appearance of These tissues subtypes have cross striations due to regular No cross striations contractile cell) arrangement of contractile organelles within their cells Type Skeletal Visceral Cardiac Contraction Voluntary Voluntary Involuntary Involuntary Location Somatic/ body Soft tissue origin. Heart and roots of Walls of visceral wall. Tongue, pharynx, great veins that organs, stomach, gut larynx, diaphragm empty into the heart tube, bronchi etc. and upper esophagus General morphology SOM.1ai.BPM1.1.FTM.3.HCB.0172 SOM.1ai.BPM1.1.FTM.3.HCB.0167 SOM.1ai.BPM1.1.FTM.3.HCB.0170 SOM.1ai.BPM1.1.FTM.3.HCB.0168 Session ID: davina1  Morphological classification According to the appearance of the contractile cells Muscle: skeletal cardiac smooth Long cylindrical cells Branched cells Spindle-shaped cells Striations Striations Centrally located nucleus Multiple nuclei Centrally located peripherally located nucleus Intercalated discs SOM.1ai.BPM1.1.FTM.3.HCB.0169; SOM.1ai.BPM1.1.FTM.3.HCB.0167; SOM.1ai.BPM1.1.FTM.3.HCB.0186; SOM.1ai.BPM1.1.FTM.3.HCB.0199 A. Skeletal Muscle Session ID: davina1  SOM.1ai.BPM1.2.MSK.1.HCB.BT.1607 Skeletal muscle histogenesis (DLA) During histogenesis mesenchymal cells form myoblasts which fuse to form a single skeletal myocyte Skeletal myocyte is therefore an elongated multinucleated syncytium syn= plus; cyte=cell  multinucleated cell This accounts for its variable length Each skeletal muscle cell = myocyte = muscle fiber Other myogenic stem cells form satellite cells which can regenerate myocytes Session ID: davina1  SOM.1ai.BPM1.2.MSK.1.HCB.BT.1607 Skeletal muscle organisation & association with connective tissue (DLA) Epimysium Perimysium Endomysium Endomysium Epimysium (E) Perimysium (P) Endomysium (En) Dense connective tissue sheath Groups of skeletal myocytes/fibers in Delicate layer of reticular fibers which encases multiple fascicles fascicle or bundle. Each fascicle is that surrounds individual muscle to form the total muscle. surrounded by a layer of connective fiber (myocyte) Contains major blood vessels tissue Contains small blood vessels and nerves Contains larger blood vessels & and very fine neuronal Essential for force nerves branches transduction Fascicles are functional units of Continues with tendon to muscle fibers that work attach muscle at the together. myotendinous junction Session ID: davina1  Skeletal Muscle organization SOM.1ai.BPM1.2.MSK.1.HCB.BT.1607 MF = muscle fibre CT = connective tissue F = fascicle E = Epimysium En = Endomysium P = Perimysium Fascicle MFN = muscle fibre nuclei FN = fibroblast nuclei Muscle fiber MFN FN Session ID: davina1 Name the structures !! ACTIVITY Session ID: davina1  SOM.1ai.BPM1.2.MSK.1.HCB.BT.1607 Name the structure 1. Epimysium 2. Perimysium 3. Endomysium MFN FN Session ID: davina1  SOM.1ai.BPM1.2.MSK.1.HCB.BT.1607 Skeletal Muscle cell (myofiber) organization Muscle fiber End myofibrils MF = muscle fibre N = nuclei C = capillary N In cross sections skeletal muscle fibers are regular shaped and encased by endomysium (End) all cells appear to be the same size and the nuclei are on the periphery never enclosed by the sarcoplasm compared to cardiac muscle Peripheral nuclei (N) located directly beneath the plasma membrane (sarcolemma)  Types of skeletal muscle cells Skeletal muscle cell is known as muscle fibre Sha'Carri Richardson Tamirat Tola Noah Lyles Sifan Hassan Classification based on enzymatic activity: Type I fibres or slow oxidative fibres (burn glucose and fatty acids), small, red full of mitochondria, large amounts of myoglobin and cytochrome complexes. These fibres have great resistance to fatigue Type IIb fibers or fast glycolytic fibers (glycogen and glucose), are large fibers, light pink, contain less myoglobin, and fewer mitochondria than type I and type IIa fibers, no good resistance to fatigue (fatigue prone) Session ID: davina1  Histological structures Muscle cell = muscle fibre = myocyte > Myofibrils > sarcomere > myofilaments (actin&myosin) Speckled profiles of cross-section through myofibrils Sarcolemma N Actin & myosin Cell sarcomere Electric cable with 1. A muscle fiber is filled with myofibrils arranged in longitudinal arrays soft wire 2. Myofibrils are specialized organelles Banded structures which extend the length of the cell The structural and functional subunit of the muscle fiber 3. Myofilaments are the contractile elements forming the myofibril Thick (myosin) and thin (actin) filaments with accessory proteins Arrangement of the thick & thin filaments creates dark and light bands that produces the cross striations characteristic of all striated muscle SOM.1ai.BPM1.1.FTM.3.HCB.0166 SOM.1ai.BPM1.1.FTM.3.HCB.0174 SOM.1ai.BPM1.1.FTM.3.HCB.0175  SOM.1ai.BPM1.2.MSK.1.HCB.BT.1009 4. Sarcomere: The smallest contractile unit of a striated muscle. It is defined as the segment of the myofibril between two adjacent Z lines. Dark or A band Light or I band S = sarcomere My = myofibrils Z = Z line Within A & I, additional bands and Mt = mitochondria G = glycogen granules lines can be observed Z line: dense line in the I band H band: less dense region in the A I band A band M line band M line: narrow dense line in the H band. Electric cable with soft wire H band WFH Pg 106 Session ID: davina1 Sarcomere  Myofilaments SOM.1ai.BPM1.1.FTM.3.HCB.0173 SOM.1ai.BPM1.1.FTM.3.HCB.0174 SOM.1ai.BPM1.1.FTM.3.HCB.0175 Myofilaments overlap each other at certain sites along the sarcomere Associated with accessory proteins Myosin: Thick filaments (1.5 μm long) Central portion of the sarcomere Actin: Thin filaments (1.3 μm long) Attach to both sides of the Z line (zig-zag) Extend into the A band to the edge of the H band Session ID: davina1  Sarcomere in different functional stages Dark or A band, median lighter H transected by an M line I A I Light or I band, median dark Z line I A I Sarcomere: resting contracted stretched I I A WFH Pg 106 Session ID: davina1 Sarcomere Sliding filament hypothesis of Huxley A band remains constant I band and H band decrease in size Z lines are drawn closer to the ends of the A bands Session ID: davina1 Clicker question!! ACTIVITY Session ID: davina1 Session ID: davina1 Name the structure A. Z line B. Myofiber C. Myofibril Muscle 1 cell or D. Endomysium Muscle fiber or E. I-band Myocyte F. A-band G. Sarcomere 7 I band 6 A-band 4 Line? Z-line 5 Sarcomere Line ? Z-line Myofibril 3 Muscle cell 2 Session ID: davina1  SOM.1ai.BPM1.2.MSK.1.HCB.BT.1610 Structure of myofilaments Thin Filaments (Actin) are polymerized G-actin forming F-actin filament Associated proteins which include: Troponin complex – Tropomyosin TnC TnI TnT F-actin (Filament) Tropomyosin – Troponin complex troponin-C (TnC) binds calcium Tropomodulin + end troponin-T (TnT) - end – binds to tropomyosin – anchors troponin complex troponin-I (TnI) – binds to actin – inhibits actin-myosin interaction Myosin molecule Thick Filaments (Myosin II) Motor proteins aggregated tail to tail to form thick myosin filaments Session ID: davina1  Session ID: SOM.MK.I.BPM1.1.FTM.3.HCB.0146 Myofilaments of the Sarcomere Myosin II/thick filament Binds to actin subunits in striated muscles to produce movement Myosin II is a dimer Head Region Connected to each other via the lever arm (S2 region) Complete myosin has 2 globular heads Forms the S1 region Project at approximate right angles from the myosin molecule A head has 2 specific binding sites One for ATP (with myosin ATPase activity) One for actin Tail region BPM1 | FTM | Lecture 35 | Muscle Tissue Opposite to the head/continuous from the S2 region Aggregated to form a bipolar thick myosin filament (in striated muscles only) “Bare zone” in the middle has no globular heads Thick myosin is connected to each other at this zone by a family of M line proteins Myosin aggregate tail-to-tail=thick myosin  SOM.MK.I.BPM1.1.FTM.3.HCB.0157//0158 Muscle Contraction Muscle contraction is a result of interaction between thick (myosin II) and thin (F-actin) filaments In skeletal muscles, many fibers contracting together results in gross movement of that particular muscle group Sliding Filament Hypothesis of Huxley Sarcomere shortens and becomes thicker, but the myofilaments remain the same length Myofilaments slide past each other Increase the amount of overlap helps them to maintain their lengths Sliding action results from repeated “make and break” attachments between the heads of the myosin molecules and neighboring actin filaments – actomyosin crossbridge BPM1 | FTM | Lecture 35 | Muscle Tissue A band remains constant I band and H band both decreases in size Z lines are drawn closer to the ends of the A bands Stages of the Contraction Cycle Attachment, release, bending, force generation and reattachment  Cross-bridge cycle (5 stages) SOM.MK.I.BPM1.1.FTM.3.HCB.0147 Resting: myosin heads are prevented from binding with actin molecules by tropomyosin Nerve stimulation: Ca2+ is released into the sarcoplasm and binds to troponin, exposing actin NO ATP myosin bound to the actin Rigor mortis lack ATP binds to the myosin: ATP Strong attachment conformational changes Myosin detach BPM1 | FTM /Lecture 35 | Muscle Tissue ATP Breakdown: 2nd conformational chan myosin head goes back Binding (weak) to original unbent position: force generation  DLA SOM.1ai.BPM1.1.FTM.3.HCB.0179 Actinomyosin crossbridge cycle and muscle contraction At the beginning of the contraction cycle, myosin head is tightly bound to actin, ATP is absent. This is a situation seen in rigor mortis https://www.youtube.com/watch?v=gJ309LfHQ3M Session ID: davina1 Molecular structure of the sarcomere  SOM.MK.I.BPM1.1.FTM.3.HCB.0143 Accessory Proteins of Skeletal Muscles Essential in regulating the spacing, attachment and alignment of the myofilaments within the sarcomere They include: Titin Extends from the Z-line toward the M line “Molecular springs” – prevents excessive stretching of the sarcomere Helps centre the thick filaments between the Z- lines α-Actinin Bundles actin filaments in parallel array Anchors actin filaments at the Z-line Desmin Intermediate filament Attaches Z-line to each other and to the plasma membrane Uses linker protein ankyrin M line proteins BPM1 | FTM | Lecture 35 | Muscle Tissue Binds thick filaments at the M line Attach titin molecules to the thick filaments eg. Myomesin, M-protein, obscurin, muscle creatine phosphatase Myosin binding protein C (MyBP-C) Stabilization of thick filaments Dystrophin Link laminin to thin filaments Absence results in Duchenne Muscular Dystrophy  Clinical correlation: Muscular dystrophy are attributed to mutations of single genes encoding several proteins of the dystrophin–glycoprotein complex Dystrophin is a rod-shaped cytoskeletal protein which links to ECM proteins laminin & agrin found in the external lamina of the myocyte associated with Duchenne and Becker’s Muscular dystrophy Dystrophin forms a complex with two groups of transmembrane proteins: 1. Dystroglycans →links dystrophin and laminin of the ECM 2. Sarcoglycans →associated with membrane dystroglycans→ associated Limb Girdle Dystrophy Congenital muscular dystrophy is a group of muscular dystrophy associated with ECM components (laminin) Session ID: davina1 SOM.1ai.BPM1.1.FTM.3.HCB.0176 SOM.1ai.BPM1.1.FTM.3.HCB.0177  Due to a defect in the gene Duchenne Muscular dystrophy coding for dystrophin associated proteins on X chromosome→ muscle fiber fragility Most common inherited myopathy A B More prevalent in males X-linked recessive Patients are unable to stand unaided in early childhood and develop progressive muscle C D weakness, becoming Normal skeletal muscle Duchenne Muscular dystrophy wheelchair- bound by their mid- teens and typically dying in In B there is breakdown of muscle fibers, which are early adult life. then removed by phagocytosis. In D muscle fibers without dystrophin are seen ( P) SOM.1ai.BPM1.1.FTM.3.HCB.0177 Session ID: davina1 SOM.1ai.BPM1.1.FTM.3.HCB.0178  Regulation of muscle contraction SOM.1ai.BPM1.1.FTM.3.HCB.0181 Myofibril: arranged in the center of the cell Triad (Td) : 1 T-tubule T-tubule + 2 terminal Sarcoplasmic reticulum (SER): forms a cisternae at the A-I junction network around the myofibrils (Ca2+ reservoir) Extends from one A-I junction to the next A-I Terminal cisterna which reservoirs of Ca2+ Transverse tubules (T-Tubule): Invaginations Nerve impulse of the sarcolemma at the A-I junction Have voltage-sensor proteins/ channels sarcomere sarcolemma activated by membrane depolarization Affect gated Ca2 channels in adjacent terminal cisternae pore Triad T-tubule Terminal How does it work? cisterna of SER Depolarization of T tubule membrane triggers release of Ca2+ from terminal cisterna & initiates muscle contraction cycle (see DLA) Session ID: davina1  SOM.1ai.BPM1.1.FTM.3.HCB.0181 Structural requirements for contraction R P Pg 325 Session ID: davina1 Motor Innervation – Neuromuscular Junction Neuromuscular Junction or motor end plate Contact between the terminal branches of an axon and a muscle fiber Axons branch as they near the muscle and Motor end plate give rise to twigs that end on individual muscle fibers (MOTOR UNIT) - All muscles within a motor unit are of the Axon branches same type ( I, IIa or IIb etc.) Covered by thin portion of external lamina ONE neuromuscular junction per muscle fiber. It Motor neuron Silver stain may branch innervating many fibers. All the muscle fibers this nerve innervates constitute a motor unit. Enters close to the origin of the muscle fiber Depolarization is propagated along the entire length in a sequential manner Each sarcomere contracts independently allowing for smooth singular action in a particular direction SOM.1ai.BPM1.1.FTM.3.HCB.0182 Session ID: davina1 SOM.1ai.BPM1.1.FTM.3.HCB.0183 Small swellings Session ID: davina1  Sensory Innervation SOM.1ai.BPM1.1.FTM.3.HCB.0185 Muscle Spindle Encapsulated sensory receptors Specialized stretch receptor located in the muscle belly Senses changes in muscle length or stretch Contains modified muscle fibers or spindle cells and neuron terminals These modified muscle fibers are surrounded by internal capsule Muscle spindle Afferent and efferent innervation Golgi tendon Golgi tendon organ organ Encapsulated proprioceptor located at Internal capsule the myotendinous junction Senses tension in the muscle fluid Sensory component of the Golgi External tendon reflex capsule Only afferent innervation  Cardiac Muscle A. Skeletal muscle B. Cardiac Muscle 1. Histological structure 2. Regulation of muscle contraction 3. Intercalated disc 4. Purkinje fibers C. Smooth muscle D. Muscle injury and repair Session ID: davina1  Histological structure SOM.1ai.BPM1.1.FTM.3.HCB.0186 SOM.1ai.BPM1.1.FTM.3.HCB.0187 SOM.1ai.BPM1.1.FTM.3.HCB.0188 Longitudinal section Cardiac muscle forms the bulk of the myocardium and extends slightly into the walls of some great vessels. Striated and has the same type & arrangement of contractile filaments as skeletal muscle (actin x myosin) cardiac myocytes are branched (), unlike SK muscle Intercalated discs(ID): dense staining cross-bands They may have one or two centrally placed nuclei The Perinuclear region (*) 1. It is free of myofibrils and contain organelles 2. It poses numerous large mitochondria & glycogen stores 3. It shows granules containing diuretic hormones: atrial natriuretic peptide and brain natriuretic peptide CT: nuclei of a connective tissue cell  Skeletal muscle Cardiac Muscle Myofibril free region Cross-sectioned cardiac muscle The branched nature leads to irregular profiles in cross-sections Nuclei appears to be enclosed by sarcoplasm V = venule CT = connective tissue A = arteriole N = nuclei Session ID: davina1 C = capillaries  Regulation of muscle contraction Sarcoplasmic reticulum – Single network along the sarcomere – Extends from Z line to Z line – Less developed than skeletal muscle – Terminal cisterna Contain Ca2+ release channels – Release Ca2+ into sarcoplasm Transverse tubular system (T tubule) – Located at the Z line (compare to skeletal muscle) – T tubules contain voltage-sensor proteins Diad – Complex of one T tubule and one Diad adjacent terminal cisternae at the Z line SOM.1ai.BPM1.1.FTM.3.HCB.0191 Session ID: davina1  Intercalated disc SOM.1ai.BPM1.1.FTM.3.HCB.0190 Intercalated discs are attachment sites between adjacent cardiac myocytes The transversely oriented parts of the intercalated disk (T) which is at M right angle to the myofibril like the risers of a stairway The longitudinal or lateral parts (L) L are parallel to myofibril like the steps of a stairway Mitochondria (M) are abundant in cardiac muscle due to the high T metabolic demands of these cells T = transversal SR = Sarcoplasmic reticulum L = Longitudinal G = glycogen granules M = mitochondria D = desmosomes FA = fascia adherence N =Gap junction (nexus) WFH Pg 120  Fascia adherens Z Transversal component FA - anchor actin filaments of the terminal sarcomere to the plasmalemma MA – anchor cell to cell, preventing their separation during contraction cycles Lateral component Gap junction – area subjected to least stress, important to spread contractile depolarization Session ID: davina1  Intercalated disc Transversal component (FA) Fascia adherens (adhering junctions) - Major structural element - Binds cardiac muscle cells at their ends - Serves as attachment site for thin filaments in terminal sarcomeres M (MA) Maculae adherents (desmosomes) - Bind individual muscle cells to each other - Reinforce fascia adherence - Found in both transverse & lateral Lateral component (GJ) Gap junctions (communicating junctions) Maculae adherents L 1 = Maculae adherents 2 = Gap junction 3 = fascia adherence T = transversal SR = Sarcoplasmic reticulum L = Longitudinal MA = Maculae adherents M = mitochondria FA = fascia adherence D = desmosomes T GJ =Gap junction WFH Pg 120  Purkinje fibers SOM.1ai.BPM1.1.FTM.3.HCB.0192 Endothelium Large, modified muscle cells located just deep to the endocardium in the subendocardial layer. Specialized to conduct impulses of the A-V bundle and allow Typical synchronization of ventricular cardiac myocytes contraction Pale staining due to: Purkinje fibers – few myofibrils ( these are located peripherally) – large amount of glycogen Abundant mitochondria Et: endothelium M: myofibrils Ec: endocardium ID: intercalated disk Pf: Purkinje fibres Mansson, trichrome stain Session ID: davina1  Smooth muscle tissue C. Smooth Muscle 1. Histological structure 2. Contractile apparatus 3. Regulation of the smooth muscle contraction D. Muscle injury and repair Session ID: davina1  Smooth Muscle Elongated, fusiform cells with tapered ends (spindle shape) – Generally organized into bundles or sheets – No cross-striations, thus even staining with H&E staining Location: Found lining tubular Respiratory and GI systems and blood vessels Usually arranged in sheets around the lumen of hollow organs Involuntary One central nucleus – Often has a corkscrew appearance in Colon H&E longitudinal section Length – ~20µm in walls of small blood vessels – ~200µm in wall of intestine – ~500µm in wall of uterus during pregnancy Session ID: davina1 RP Pg 335  Smooth muscle – structure Smooth muscle fibres are often referred to as spindle shaped In histological sections this feature results in differing diameters and some myocytes not having nuclear profiles Session WFH Pg 113ID: davina1  Smooth muscle - structure SOM.1ai.BPM1.1.FTM.3.HCB.0194 Smooth muscle cells are interconnected with gap junctions (GJ) or nexus – Communicating junctions – Small molecules & ions pass from cell to cell – Provide communication links to regulate contraction of entire bundle or sheet Pinocytotic vesicles (PV) Dense bodies contraction apparatus Sarcoplasmatic reticulum (SR) Smooth muscle (SM) cells secrete connective tissue matrix ‒ Well-developed rER & Golgi & mitochondria ‒ Synthesize both type IV & III collagen fiber ‒ Elastin, proteoglycans, and multi-adhesive glycoproteins ‒ Vascular and uterine SM also secrete large amounts of type I collagen and elastin Session ID: davina1  Smooth muscle contractile apparatus SOM.1ai.BPM1.1.FTM.3.HCB.0195 – Thick filaments contain: Myosin II – Thin filaments contain: Side polar thick filament Actin Tropomyosin (no associated troponin) Caldesmon and Calponin bind to Actin proteins blocking the myosin binding site – Dense bodies (cytoplasmic densities) which attach thin and intermediate filaments Contain α-actinin Dense body – Accessory proteins α-actinin (see dense bodies) Myosin light chain kinase (MLCK): initiates contraction Calmodulin - Ca2+ binding protein Ca2+ -calmodulin complex binds & activates MLCK Session ID: davina1 Smooth Muscle - contraction Dense body Myosin (thick) and actin (thin) filaments form a crisscross lattice. The thin filaments are anchored to cytoplasmic and membrane relaxed density bodies Density bodies Contracted (corkscrew nucleus) densities (dense bodies), which are then associated with small and intermediate filaments, such as Dense bodies vimentin and desmin Dense bodies contain α-actinin During contraction, the thin filaments slide past the thick filaments. Actin-myosin shortening, pull on the dense bodies. This arrangement pull the ends toward the center. The cell adopts a globular shape and the nucleus adopts a “corkscrew” shape SOM.1ai.BPM1.1.FTM.3.HCB.0196 Session ID: davina1  SOM.1ai.BPM1.2.MSK.1.HCB.BT.0195 Smooth muscle contractile apparatus Vascular S Muscle:Pinocytic vesicles (PV), Basal lamina (BL) a-actinin dense bodies Dense bodies No T tubule system - Analogs of Z lines in striated muscle Its analogous system consists of: - Distributed throughout the sarcoplasm in a - Caveolae→ Invaginations of cell network of intermediate filaments membrane (caveolae Latin = little caves) Desmin - Sarcoplasmic reticulum Vascular smooth muscle contains - Cytoplasmic vesicles vimentin in addition to desmin  Smooth Muscle Contraction Ca+2 Sarcolemma depolarization calmodulin Inactive myosin II hormone calmodulin complex bind to actin active myosin II Myosin light chain kinase Conformation change Contraction is regulated by the Ca2+-calmodulin-MLCK system 1. Increase in Ca2+ concentration in the sarcoplasm 2. Ca2+ binds to calmodulin forming the Ca2+ -calmodulin complex 3. Ca2+ -calmodulin complex binds MLCK 4. MLCK phosphorylates regulatory light chain of myosin 5. Actin-binding site of myosin head is activated & attaches to actin Session ID: davina1 SOM.1ai.BPM1.1.FTM.3.HCB.0196  SOM.1ai.BPM1.2.MSK.1.HCB.BT.1710 Regulation of smooth muscle contraction Contraction in smooth muscles is initiated by a variety of impulses, including…elevating the intracellular concentration of Ca2+ Mechanical Passive stretching of vascular smooth muscle activates myogenic Electrical reflex Electrical depolarization Neural stimulation leading to release of Ach and norepinephrine Mechanical Chemical Chemical Angiotensin II, vasopressin, thromboxane A2 Use second-messenger pathways such as IP3 and NO- cGMP pathways. Ca2+ Latch state is the sustained muscle contraction. The myosin head remain attached to actin for longer time with less energy expenditure as ATP is required for detachment. SOM.1ai.BPM1.1.FTM.3.HCB.0196