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Muscle Tissues
Organisation of the Body
| Question | Answer |
|---|---|
| Main tissues of the body | Connective - fixed and wandering - support and protection Muscle - elongated contractile cells - movement Nervous - intertwining elongated processes - transmission of nervous impulses Epithelium - aggregated polyhedral cells - covering, absorption |
| Type and use of contractile elements | Nearly all cells have contractile elements made of actin and myosin Used for cells to move, change shape and for intracellular movement of organelles |
| What makes muscle special | Muscle is made up of cells where the contractile machinery is permanently orientated This permits directional movement and contractions appropriate to that tissue |
| What does muscle allow to happen | Movement Change posture Pump blood around the body Movement of internal organelles Regulate blood pressure |
| Three main types of muscle | Skeletal Cardiac Smooth |
| Characteristics of skeletal muscle | Attached to bones Crossing joints Controlling eye Striated Multiple, peripherally located nuclei Innervated by voluntary somatic neurons |
| Characteristics of cardiac muscle | Found in the heart Striated Usually one centrally located nuclei Innervated by involuntary, autonomic neurons |
| Characteristics of smooth muscle | Found in visceral organs including blood vessels and glands Non-striated Single, centrally located nucleus Innervated by involuntary, autonomic neurons |
| Contraction in different muscle types | All types of muscle generate contractile forces based on actin and myosin These are different in amino acid sequence, arrangement in the cell and in association with different sets of proteins to control contraction |
| Specific muscle organelles | Cell membrane - sarcolemma Cytoplasm - sarcoplasm Smooth endoplasmic reticulum - sarcoplasmic reticulum Mitochondria - sarcosomes Contractile unit - sarcomere |
| Skeletal muscle | Around 40% of the body Approx. 650 skeletal muscles in a human Most attach to bones via tendons (bands of collagen fibres) Designed for voluntary movement |
| Development of skeletal muscle | Somite cells induced to divide and differentiate into sclerotome and dermomyotome Induced by sonic hedgehog protein from embryonic notochord Then forms Paz3+/7+ Expressing myoblasts withdraw from cell cycle and express MyoD and Myf5 - muscle TFs |
| Pax3+ and Pax7+ | Release muscle cell precursors during development Produce: Embryonic and fetal myoblasts and satellite cells |
| Structure of mature skeletal muscle | Progenitors give rise to myoblasts which fuse to form multinucleated myotubes These develop into mature tubular cells - multinucleate syncytium Myofibers manufacture myofibrils composed of microfilaments |
| Multinuclear nature of skeletal muscle | Nuclei are peripherally located 10-100 um diameter, up to 35cm long |
| Satellite cells | Regenerative cells located on the surface of skeletal muscle |
| Blood vessels to skeletal muscle | Penetrate the muscle and form a rich capillary network Runs between and parallel to the muscle fibres |
| Microfilaments | Myofilaments are made of actin and myosin Thin and thick filaments repeat along the length of the myofibril Sarcomere - repetitive subunits of contractile apparatus between z lines Gives a banding pattern to myofibrils |
| Sarcomere | Thick filaments - occupy A band I band - Thin filaments Thick filaments have one end attached to the z-line by titin Think filaments attached to z-line by alpha actinin H band - centre of thick band M line - connections between thick filaments |
| Skeletal muscle contraction | Z disks brought closer together - filaments do not shorten Reduces width of I and H bands - without influencing width of A band In mammalian skeletal muscle each thick filament is surrounded by six thin filaments |
| Thick filament | Myosin II 6 polypeptides twisted to form a fibre helix with globular ends which have ATPase activity and bind to actin |
| Thin filament | G-actin Globular protein which polymerises into polymeric fibres and contains a myosin binding site |
| Tropomyosin | Fibre like protein which wraps helically around the thin G-actin filament In relaxed muscle this blocks attachment site for myosin crossbridge, thus preventing contraction |
| Troponin | Calcium sensitive globular protein complex attached to end of each tropomyosin molecule Ca binds to knock tropomyosin off the binding site and initiate the contraction cycle |
| Titin | Links myosin to z-line Molecular spring for passive elasticity of the muscle Maintains sarcomere architecture Largest known protein |
| Nebulin | Actin binding protein localized to thin filament regulating its length |
| Energy for contraction | Muscular energy accounts for most of the bosies energy consumption Stored ATP/creatine - 8-10 secs Glycolysis - 90 secs Aerobic respiration - 2 mins+ |
| Rigour mortis | When cells are unable to manufacture ATP dissociation of thick and thin filaments cannot occur and rigor mortis sets in Myosin heads remain bound to active sites of actin until the muscle decomposes Can be used to estimate time of death |
| Types of skeletal muscle | Fibre types controlled by frequency of impulses from associated motor nerve Type 1 - slow Type 2 - fast Mixture in most human muscles Can distinguish biochemical and metabolic differences histochemically |
| Slow twitch muscle | Aerobic/slow - have abundant mitochondria and extensive blood supply for high endurance |
| Fast twitch muscle | Anaerobic metabolism - have abundant glycogen for short bursts of energy - low endurance IIA - intermediate between type I and II IIB - classic type II fast - high rate of contraction |
| T-tubules | Invaginations of the sarcolemma into cell System of t-tubules surround each myofibril Juxtaposed to sarcoplasmic reticulum Sarcoplasmic reticulum displays dilated termina cisternae |
| Triads | Two cisternae in a close apposition to a t-tubule Impulse is conveyed from t-tubules to cisternae mechanically Triggers calcium release Troponin binds to it and activates myosin by knocking tropomyosin off binding site |
| Motor end plate | Somatic motor nerves terminate on skeletal muscles at neuromuscular junctions Responsible for initiation of action potentials across the muscles surface One motor neuron can supple many muscle cells to form a motor unit Allows contraction in unison |
| Neuromuscular junction | Nerve action potential opens voltage gated calcium channels Entry of Ca triggers fusion of synaptic vesicles containing acetylcholine with plasma membrane Ach binds and opens postsynaptic channels on the muscle which triggers and AP |
| Endomysium | Surrounds each muscle fibre Composed of reticular fibres and external lamina (basement membrane) |
| Perimysium | Surrounds bundles (fascicles) of muscle fibres (20-60 per fascicle) Dense collagenous connective tissue derived from epimysium |
| Epimysium | Surrounds entire muscle Dense irregular collagenous connective tissue Collage transmits mechanical force generated from contraction |
| Dystrophin associated glycoprotein complex | Connects cytoskeleton of muscle fibre to surrounding extracellular matrix through cell membrane Genetic defects associated with muscular dystrophy |
| Dystrophin | Rod shaped cytoplasmic protein and vital part of protein complex Maintains mechanical integrity of cell during contraction by anchoring cytoskeletal elements Absence of this means force is no longer transmitted from myocytes so bone cannot move at joint |
| Duchenne muscular dystrophy | Fatal x-linked disorder Effects 1 in 3500 new-born males Caused by mutations in the dystrophin genes causing a frame shift. Leads to truncated unstable dystrophin- impairment of sarcolemma Symptoms - muscle weakness and wasting |
| Genomic organisation of dystrophin gene | Largest known human gene 2.4 mb Primary transcript 2100 Kb - mature mRNA 14 Kb 79 exons code for protein of 3685 amino acids Produces a range of transcripts encoding many isoforms |
| Mutations in dystrophin gene | 60-65% deletions 5-15% duplications Point mutations1/3 cases caused by de novo mutation |
| Treatments for DMD | Corticosteroids Physiotherapy Cardiac and respiratory support Palliative care Genetic counselling |
| Becker muscular dystrophy | Related disorder Becker muscular dystrophy has a milder phenotype Shortened transcripts of DMD gene allow for expression of limited amounts of internally truncated but partially functional protein In frame mutation |
| Novel treatments for DMD | Delivery of normal dystrophin gene - mini and micro forms Exon skipping - anti-sense oligonucleotides - shorter protein Utrophin upregulation |
| Challenges of gene replacement for DMD | Size of gene - mini and micro dystrophins Delivery to all muscles - viral vectors |
| Antisense oligonucleotide based exon skipping therapy | Chemically modified single stranded nucleic acids Relatively short and hybridizes to unique sequence Bind to mRNA to modify its exon content - skips problematic exons Called antisense oligonucleotide and sequence is complementary to genes mRNA |
| Upregulation of utrophin for DMD | Utrophin is a closely related gene Encodes protein of similar size and structure Expression tightly regulated - immature muscle and at NMJ Identify small drugs to activate promotor and allow functional substitution of dystrophin |
| Neuromuscular diseases | Problems with nervous system cause spasticity or paralysis depending on location and nature of problem Include - motor neuron disease, cerebrovascular accident, Parkinson's and myasthenia gravis Can lead to problems with movement or motor coordination |
| Satellite cells in muscle regeneration | Normal muscle fibre with myonuclei and satellite cell Damaged muscle activates satellite cell (proliferated) Muscle precursor cells fuse together and repair damage Regenerated muscle fibre develops new satellite cells and new myonuclei |
| Cardiac muscle development | Derived from defined mass of splanchnic mesenchyme and myoepicardiaum mantel Give rise to epicardium and myocardium Endocardium arises from vascular endothelial progenitors |
| Cardiac muscle | Specialised branched striated muscle Arranged in layers - laminae Usually have single, centrally located nuclei Abundant mitochondria and extensive t-tubule network Intercalated disks - transverse and lateral connections between cells |
| Coupling between cardiac myocytes | Intercalated discs interface between adjacent cells - support synchronised contraction Three main types Fascia adherens - anchoring sites for actin Macula adherens - bind cells together Gap junctions - allows ion to pass through |
| Intercalated disc | Conducts electrochemical potentials directly between cells via gap junctions Cell length 100um Highly resistant to fatigue - many mitochondria and good blood supply Self excitable - myogenic |
| Cardiac excitation contraction coupling | Following membrane depolarisation Release of calcium from sarcoplasmic reticulum Subsequent ca induced myofilament activation Myocardial contraction activated by transient rise in cytosolic calcium conc to 1 Mm from resting diastolic of 0.1 uM |
| Purkinje fibres | Specialise myocardial fibres located in inner ventricular walls beneath endocardium Specialised conducting fibres larger than cardiomyocytes Carry impulse from SAN to ventricles - synchronised contraction Pale staining fibres |
| Myocardial infarction | Blood vessels supplying heart become obstructed causing death of tissue Treated by stent or bypass May be possible to repair with stem cells iPS cells can differentiate into cardiomyocytes under appropriate conditions |
| Dilated cardiac myopathy | Heritable or idiopathic form of heart failure Mutations in cytoskeleton disrupt intercalated disks as dissociate junctions between myocytes and contractile function Leads to enlargement of the heart and thinning of ventricular walls - weakens pumping |
| Hypertrophic cardiac myopathy | Autosomal dominant family disorder Mutation in sarcomeric proteins results in defective contraction Abnormal growth and hypertrophy of cardiac muscle Leads to ventricular wall thickening and less effective pumping |
| Low regeneration of cardiomyocytes | Cardiomyocytes slowly turned over with age Less than 50% replaced in a normal life span At 20 - 1% renewal/year At 75 - 0.4% renewal/year Recent research focussed on enabling cardiomyocytes to re-enter cell cycle |
| Hippo pathway - kinase cascade | Prevents adult cardiomyocyte proliferation and regeneration upregulated human heart failure Blocking hippo induces repair program Previously unrecognised capacity for repair |
| Smooth muscle | Elongated, spindle shaped, non-striated, mononucleate cells Enclosed by basal lamina and network of reticular fibres Cells fusiform - elongated cells that taper at either end Connective tissue layers not as well seen in smooth muscle as thinner |
| Arrangement of filaments in SM | Actin and myosin form a lattice like network but contract by sliding filament mechanisms similar to striated muscle |
| Focal densities | Attachment junctions - attach actin to sarcolemma |
| Dense bodies (alpha actin) | Attach intracellular actin filaments to each other functionally analogous to z-lines Maintain alignment of thin filaments |
| Caveolae | Involved in fluid and electrolyte transport Analogous to T-tubule system in skeletal muscle Transmit depolarisation signal Can be stimulated to contract by nervous signalling or can contract in response to spontaneous APs |
| Gap junctions and adherns junctions | Communication and mechanical coupling Desmosomes mechanically link cells Gap junctions couple adjacent cells chemically and electrically Facilitate spread of chemicals or action potentials between smooth muscle cells |
| Where is smooth muscle found | Lining of viscera in gut, bladder, uterus, respiratory system and blood vessels Spindle shaped cells loosely arranged in the uterus but regularly arranged in the bowel |
| Single unit SM | Unitary function enabled by electrical coupling via gap junctions Allows muscle to behave as a syncytium e.g. GI tract or bladder |
| Multiunit SM | Each cell isolated and stimulated independently to enable finer control e.g. iris of eye |
| Circular and longitudinal smooth muscle in the gut | In intestine smooth muscle forms 2 layers Longitudinal runs along and circular runs around the gut They cause wave like peristalsis which propels the contents Circular causes segmentation by wave like contractions Longitudinal causes propulsion |
| Contraction of smooth muscle | Does not contain troponin Contraction regulated by phosphorylation of myosin light chains Calcium ions from outside released from caveolae bind to calmodium Phosphorylated regulatory chain increases ATPase, light chain binds to actin |
| Axons in the autonomic nervous system | Do not form NMJs with smooth muscle A series of neurotransmitter filled bulges called varicosities loosely form motor units A varicosity releases NTs into synaptic cleft Visceral muscle pacesetter cells spontaneously trigger APs and contraction |
| Abnormalities of smooth muscle | Can undergo hyperplasia and hypertrophy Asthma due to sustained contraction of bronchial smooth muscle Hypertension due to contraction of vascular smooth muscle In atherosclerosis arterial smooth muscle cells accumulate cholesterol |
| Smooth muscle regeneration | Greatest capacity to regenerate of all muscle cell types Retain ability to divide and can increase in number e.g. in a pregnant uterus New cells produced by division of pericytes that lie along small blood vessels Can also hypertrophy |
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