Successive magnifications

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2 Successive magnifications Skeletal ("striated" = striped) muscle cell ("fiber" = cell) microns (huge) and long (tendon to tendon) There are smaller units within fiber called "myofibrils" (1-2 microns in cross section) Thus myofibrils/fiber

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4 Fine structure Sarcomeres - units along myofibrils striped (striated) pattern is in register Within the myofibrils are the filaments Actin - G (globular) polymerizes to F (filamentous) actin - the thin filament Myosin - (2 heavy chains and 4 light chains) - the thick filament I-band (isotropic - light), A-band (anisotropic, dark)

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8 Proteins Z disc where actins are joined line in the middle of the myosin A (anisotropic)= where myosin is I (isotropic) where actin is but not myosin H (helle) (lighter) where there is myosin but not actin This figure shows titin a gigantic protein that is elastic

9 Muscular dystrophy (Duchenne) X-linked recessive (sexlinked), affects boys Lethal by age 20 "Dystrophin" protein associated with muscle cell membrane, binding cytoskeleton with extracellular matrix.

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13 Sliding filaments H Huxley and AF Huxley length tension curve shows optimum (good overlap without the actin colliding) (note, there will be an important difference for heart muscle.)

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16 ATP myosin rowing through sea of actin ATP binding unhooks myosin from actin rigor mortis (box p. 348) - a "stiff" ATP has run out, actin and myosin are locked ATP -> ADP, phosphate added to the myosin like the rower back-stroking When phosphate kicked off, myosin and actin bind, followed by the power stroke

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18 Ca2+ Ca2+ ions released for contraction tropomyosin on actin troponin has a Ca2+ binding site like calmodulin Ca2+ binding to troponin pulls tropomyosin off of actin's binding sites for myosin

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22 Neuromuscular junction Action potential from nerve opens channels (nicotinic acetylcholine receptors) "synapse" called the neuromuscular junction. (Notice that the nerve branches.) big "synapse" - it works (excitatory In TEM, note folds, increasing the area on the muscle cell. Note the space with electron density in the cleft. Note the numerous vesicles.

23 Quanta = vesicles Bernard Katz70 Nobel prize quantal transmission at neuromuscular junction. quanta are individual vesicles neuromuscular junction is like any synapse except bigger and easier to study. information could fit here or in synapse lecture Decrease Ca2+ to reduce vesicle release

24 Myasthenia gravis autoimmune attack on nicotinic receptors Muscle weakness eyelid droop Give AChE inhibitor neostigmine to ameliorate symptoms

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27 Pharmacology nicotine is an agonist there are pharmacological antagonists (curare, a plant alkaloid from Clondodendron tomentosum) Important for mechanisms of muscular relaxatants used in surgery (like succinylcholine) Must relax muscles in surgery but must prove that anesthesia is adequate.

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30 Lou Gehrig s disease Amyotropic Lateral Sclerosis (ALS) disease affects spinal motor neurons some cases familial led to identification on chromosome 21 coper/zinc Super Oxide Dismutase (SOD1) reduces oxygen radicals

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32 Motor units how many muscle cells per motor neuron 13 eye 1730 calf

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34 Muscle action potential action potential goes down muscle cell But cell is too big. So transverse tubules (T tubules) get action potential into cell at numerous locations (for each sarcomere and for each myofibril). Proximity with a specialized smooth endoplasmic reticulum called the sarcoplasmic reticulum causes release of Ca2+.

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38 Excitation (summary) ACh to synapse Ecxitation to spike Final common pathway action potential in membrane and t-tubules, t=transverse Ca++ release from sarcoplasmic reticulum (ER) T at A-I junction in Skeletal muscle but it is at the z line in cardiac muscle and in frog skeletal muscle

39 Types of muscle Difference obvious in turkeys Fast twitch, strong, anaerobic, white meat Slow twitch, enduring, aerobic, dark meat capillaries (hemoglobin), myoglobin, cytochromes in mitochondria can alter with training stain, for ATPase, to show mixed muscle cells in a muscle (dark is slow, aerobic).

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44 Metabolism muscle uses glucose and fatty acids (from plasma) and glycogen and triglyceride (from muscle) Glycogen -> (glycogenolysis) -> glucose Overall, 1 glucose can give up to 38 ATP's, a few from glycolysis and the rest from the mitochondrion

45 Anaerobic glycolysis Without oxygen, make ethanol (yeast) or lactate (lactic acid) [muscle] Anaerobic glycolysis is used to deliver ATP quickly but wastefully (squandering glucose). Make ATP's but need to regenerate NAD+ [from NADH] to make.

46 Lactic acid Lactic acid contributes to fatigue in muscle and oxygen debt the liver eventually reconverts. Anaerobic cellular "respiration" is needed in times of extreme exertion because the heart (cardiac output) is the limiting factor in delivery of oxygen to muscle. Lactic acid is also made by bacteria in yogurt, sour cream, and cheese.

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49 Monitoring stretch remember reflex from synapse lecture knee-jerk reflex - tap patellar ligament, spindle (stretch receptor) alpha motoneuron to muscle gamma motor neuron goes to nuclear chain fibers (intrafusal muscle) to set tone on spindle sensory fiber wraps around nuclear bag fiber

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