skeletal muscle - colorado.edu€¦ · skeletal muscle makes up 40 % of body mass smooth muscle,...
TRANSCRIPT
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Skeletal Muscle
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Outline
❚ Structure❚ Molecular mechanism of contraction❚ Molecular characteristics of contractile
proteins❚ Interaction between myosin and actin on
muscle contraction❚ Neuromuscular junction
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Skeletal muscle
❚ Skeletal muscle makes up 40 % of body mass❚ Smooth muscle, cardiac muscle, make up 5-10 % of
body mass
❚ Skeletal muscle- voluntary contraction, striated, multi-nucleate, terminal cell type
❚ Smooth muscle-involuntary contraction, non-striated, uninucleate, can undergo mitosis
❚ Cardiac muscle, involuntary contraction, striated, uni- or binucleate nuclei, slow dividing, terminal cell type
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Nomenclature
❚ Sarcolemma- plasma membrane❚ Sarcoplasmic reticulum- endoplasmic
reticulum❚ Muscle fiber- cell❚ Myofibril-subcellular fibers❚ Sarcomere - functional unit of myofibril
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Muscle zones
❚ A band = thick and thin filaments❚ I band = thin filaments only❚ Z line = actin attachment point❚ H band = thick filaments only
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Molecular Mechanism of Contraction
❚ Sliding filament theory of contraction❙ Shortening of the sarcomere is caused by
increased overlap between thick and thin filaments, not shortening of thick and thin filaments
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Sliding Filament Theory of Muscle Contraction
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Optimal overlap between thick and thin filaments
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Molecular Characteristics of Contractile Filaments
❚ Myosin (thick filament)❙ actin binding domain❙ ATPase site❙ ATP binding❙ molecular hinges
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Myosin:•Actin binding site•ATP/ADP binding sites•ATPase site
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Actin (thin) filament
❚ Polymerized chain of G actin - called filamentous actin (F actin). Double helix
❚ tropomyosin- wraps around actin, covers myosin binding domain
❚ troponin- 3 subunits attached at periodic locations along tropomyosin fiber❙ tropomysin binding domain❙ calcium binding domain
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Interaction Between Actin and Myosin to Cause Contraction
❚ Pure actin and myosin will bind to each other readily❚ If troponin-tropomyosin complex added, inhibits actin
and myosin binding, therefore active binding sites on actin filament are blocked by troponin-tropomyosin complex
❚ When calcium ions bind to troponin, active binding sites are uncovered and conformational change allows myosin to bind to actin
❚ As sites become uncovered, myosin binds to actin
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Cross-bridges on either side of the thick filament face each other.
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isometricisotonic
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Excitation-contraction coupling❚ All muscle tissue is irritable,ie.,
depolarizes when electrically stimulated❚ Nicotinic cholinergic receptors on the
sarcolemma are ligand-regulated Na+
channels❚ Therefore, when Ach binds, Na+ enters
and muscle depolarizes❚ The motor nerves innervating skeletal
muscle originate in the ventral horn of the spinal cord (somatic motor NS) and are cholinergic
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Motor unit=motor nerve and fibers that it innervates. One motor nerve may innervate 100 muscle fibers, but each muscle fiber is innervated by only one nerve
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End plate potential
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T-tubules
❚ Application of small amounts of electrical current around Z line, but not other areas, is capable of producing a contraction
❚ Anatomical studies in frog muscle indicated a series of sarcolemma invaginations that carry current to inner myofibrils- T-tubules
❚ Each T-tubule bordered on either side by swollen region of sarcoplasmic reticulum, lateral or terminal cisterna(e);together this structure is called a triad
❚ Cardiac muscle similar, 1 T-tubule and 1 lateral cisterna = Diad
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AP causes Ca2+
channels in SER to open
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Neuromuscular junction
❚ Specialized synapses between cholinergic motor neurons and skeletal muscle
❚ Each motor neuron may innervate 1-100 individual muscle fibers
❚ Each muscle fiber innervated by only one motor neuron
❚ 1 motor neuron and all muscle fibers it innervates is called a motor unit
❚ Acetylcholinesterase- enzyme in the cleft that degrades acetylcholine
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Recruitment of Motor Units
❚ Each muscle fiber contracts in an “all-or-nothing” fashion
❚ If so, then how do whole muscles contract in a graded or proportional fashion?
❚ Answer: Differential recruitment of motor units.
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Clinical Correlations
❚ Drugs that interfere with neuromuscular junction❘ nicotine- binds irreversibly to nicotinic receptors❘ Acetylcholinesterase inhibitors- neostigmine,
prolonged muscle contraction❘ Curare- poison dart frog skin, blocks Ach
receptors, muscle relaxation❙ Strychnine- inhibits glycine input to motor neurons in
spinal cord. Normally, glycine inhibits motor neurons. Strychnine causes disinhibition of motor neurons, over-activation of motor neurons and convulsions
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Clinical Correlations (con’t)
❚ Amyotrophic lateral sclerosis (ALS)- Also known as Lou Gehrig’s disease. Scar tissue forms around motor neurons causing death of motor neurons and muscle weakness. 90% of cases have no cause
❚ Myasthenia gravis- autoimmune disease that attacks muscle nicotinic receptors
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ATP conservation
❚ If muscle is stimulated, ATP levels don’t change
❚ Creatine phosphate is a muscle storage form of phosphate
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Cardiac muscle
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