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1 Muscles Ch.12

2 Our patient for the day...

3 Name: Eddy Age: Newborn Whole-body muscle contractions No relaxation Severe difficulty breathing due to inadequate relaxation of breathing muscles Diagnosed with tetanus

4 Stepping on a rusty nail with a certain type of bacteria can be baaaaaad Let s talk about why.

5 Our patient for the day...

6 Name: Eddy Age: Newborn Whole-body muscle contractions No relaxation Severe difficulty breathing due to inadequate relaxation of breathing muscles Diagnosed with tetanus

7 Signaling a muscle to start contraction ACh Nicotinic receptor CNS Target: skeletal muscle

8 Figure 8.19a ESSENTIALS Synaptic Communication Neurotransmitter Release An action potential depolarizes the axon terminal. Action potential arrives at axon terminal Synaptic vesicle with neurotransmitter molecules The depolarization opens voltage- gated Ca 2+ channels, and Ca 2+ enters the cell. Docking protein Ca 2+ Synaptic cleft Calcium entry triggers exocytosis of synaptic vesicle contents. Neurotransmitter diffuses across synapse and binds to post-synaptic receptors. Neurotransmitter binding initiates a response in the postsynaptic cell. Postsynaptic cell Voltage-gated Ca 2+ channel Cell response Receptor If this

9 Somatic Motor Pathways Trigger Action Potentials Within Skeletal Muscle Synaptic vesicle (ACh) Ca 2 + Ca 2 + ACh Voltage-gated Ca 2 + channels Acetyl + choline AChE Nicotinic receptors bind ACh, opening Na+ channels, triggering action potentials and contraction in skeletal muscle. Skeletal muscle fiber

10 Why do APs in the muscle cause them to contract?

11 To learn about something s function, we can start by taking a look at its structure. Let s take a look under the microscope

12 Anatomy review

13 Skeletal muscle composed of many of muscle fibers/cells Tendon (connects bone to muscle) Skeletal muscle Nerve and blood vessels Connective tissue Muscle fascicle: bundle of fibers Connective tissue Nucleus Muscle fiber

14 Skeletal muscle composed of many of muscle fibers/cells Whole muscle Muscle fascicle Tendon (connects bone to muscle) Skeletal muscle Nerve and blood vessels Connective tissue Muscle fiber/cell Muscle fascicle: bundle of fibers Connective tissue Nucleus Muscle fiber

15 Figure 12.1 THE THREE TYPES OF MUSCLES HAVE DIFFERING STRUCTURES/APPEARANCES Skeletal muscle fibers are large, multinucleate cells that appear striated (striped) under the microscope. Control the movement of our skeleton Nucleus Muscle fiber (cell) *multinucleated=many nuclei in same cell Cardiac muscle fibers are also striated but they are smaller, branched, and uninucleate. Cells are joined in series by junctions called intercalated disks. Striations Nucleus Muscle fiber Intercalated disk Striations Smooth muscle fibers are small, uninucleate, and lack striations. Nucleus Muscle fiber

16 The basic functional unit of a myofibril is the sarcomere A band Sarcomere Z disk Z disk ANATOMY SUMMARY Myofibril M line I band H zone Titin Z disk M line Myosin crossbridges Z disk Thick filaments M line Thin filaments A band: overlap of thick and thin filaments I band: only thin filaments Titin Myosin heads Troponin Nebulin Myosin tail Hinge region Tropomyosin G-actin molecule Myosin molecule Actin chain

17 The basic functional unit of a myofibril is the sarcomere A band Sarcomere Z disk Z disk ANATOMY SUMMARY Myofibril M line I band H zone Titin Z disk M line Myosin crossbridges Z disk M line Thick filaments Thin filaments Titin Myosin heads Troponin Nebulin Myosin tail Hinge region Tropomyosin G-actin molecule Myosin molecule Actin chain

18 Muscle cells and tissue use unique names for some common things

19 End anatomy review

20 Muscle fibers composed of subunits called myofibrils Mitochondria (energy source) Sarcoplasmic reticulum Nucleus Thick filament Thin filament T-tubules Sarcolemma Now let s look at one individual muscle fiber/cell and its part Myofibril Sarcolemma=Cell membrane Sarcoplasmic Retic.=Modfied Endoplasmic Reticulum T-tubules=invaginations of sarcolemma

21 Muscle fibers composed of subunits called myofibrils Sarcoplasmic reticulum (Ca2+ storage) Mitochondria (energy source) Nucleus T-tubules Sarcolemma (cell membrane) Sarcolemma=Cell membrane Sarcoplasmic Retic.=Modified Endoplasmic Reticulum T-tubules=invaginations of sarcolemma

22 2013 Pearson Education, Inc. Figure 12.10a ESSENTIALS Excitation-Contraction Coupling and Relaxation Slide 2 Axon terminal of somatic motor neuron KEY DHP = dihydropyridine L-type calcium channel Muscle fiber T-tubule Z disk Actin Action poten t ial ACh Let s look in a bit more detail about how calcium gets released from the Somatic sarcoplasmic motor neuron releases Na + ACh a neuromuscular junction. reticulum... RyR DHP Ca 2+ Motor end plate Troponin Tropomyosin Myosin head Sarcoplasmic reticulum M line RyR = ryanodine receptor-channel Net entry of Na + through ACh receptor-channel initiates a muscle action potential. Myosin thick filament

23 Figure 12.4 T-TUBULES HELP SPREAD ACTION POTENTIAL IN FIBER T-tubules are extensions of the cell membrane (sarcolemma) that associate with the ends (terminal cisternae) of the sarcoplasmic reticulum. T-tubule brings action potentials into interior of muscle fiber. AP in muscle fiber Sarcoplasmic reticulum stores Ca 2 +. Sarcolemma Triad Thick filament Thin filament Terminal cisterna

24 Figure 12.10b ESSENTIALS Excitation-Contraction Coupling and Relaxation Slide 5 DHP KEY DHP = dihydropyridine L-type calcium channel DHP RyR RyR = ryanodine receptor-channel Action potential in t-tubule Let s look in a bit more detail alters conformation about of how DHP receptor. DHP doesn t open! calcium gets released from the sarcoplasmic RyR reticulum... DHP receptor opens RyR Ca 2+ release channels in sarcoplasmic reticulum, and Ca 2+ enters cytoplasm. Ca 2+ released Ca 2+ binds to troponin, allowing actin-myosin binding. Myosin thick filament Myosin heads execute power stroke. Distance actin moves Actin filament slides toward center of sarcomere Pearson Education, Inc.

25 Figure 12.8b (2 of 7) Figure 12.10b ESSENTIALS Excitation-Contraction Coupling and Relaxation Slide 5 Slide 5 Power stroke Cytosolic Ca 2+ TN DHP RyR DHP Action potential in t-tubule Let s look in a bit more detail Troponin-Ca alters conformation about how 2+ of DHP receptor. complex DHP pulls doesn t open! calcium gets released from the tropomyosin sarcoplasmic Actin DHP receptor opens RyR Ca RyR away from actin s reticulum moves release channels in sarco- P i ADP Tropomyosin shifts, exposing binding site on actin. Ca 2+ released Myosin thick filament Ca 2+ levels increase in cytosol. KEY DHP = dihydropyridine L-type calcium channel Ca 2+ binds to troponin (TN). RyR = ryanodine receptor-channel myosin-binding site. plasmic reticulum, and Ca 2+ enters cytoplasm. Ca 2+ binds to troponin, Myosin allowing actin-myosin binds strongly binding. to actin and completes power stroke. Myosin heads execute power stroke. Distance actin moves Actin filament moves. Actin filament slides toward center of sarcomere. See video for how myosin uses ATP to complete power stroke 2013 Pearson Education, Inc Pearson Education, Inc.

26 After death, an animal can experience rigor mortis, the state of rigidity due to sustained muscle contraction...even after death. Rigor mortis is due to lack of production of ATP. WTH?! NO ATP leads to sustained muscle contraction?!?! Let s watch the video again...

27 A normal muscle cell at rest (no sarcoplasmic Ca2+, ATP hydrolyzed into ADP + P by myosin) Ca 2+ released Ca 2+ not released A normal excited, muscle cell (sarcoplasmic retic. Ca2+ released) Binding sites for myosin unexposed, No contraction

28 A normal excited, muscle cell (sarcoplasmic retic. Ca2+ released) Myosin binds to actin ATP present? Myosin detaches and hydrolyzes ATP. Myosin resets If Ca2+ still around too, generate another power stroke Myosin releases ADP and P, generates power stroke/force

29 A normal excited, muscle cell (sarcoplasmic retic. Ca2+ released) Rigor mortis: hours after death, SR membrane breaks down. Myosin binds to actin Sarcoplasm Ca 2+ Force generated Available ATP Myosin gets stuck in this conformation Myosin releases ADP and P, generates power stroke/force

30 A normal excited, muscle cell (sarcoplasmic retic. Ca2+ released) How do we get the muscle to relax normally? Myosin binds to actin Myosin releases ADP and P, generates power stroke/force

31 Figure 12.10b 12.10c ESSENTIALS Excitation-Contraction Coupling Coupling and and Relaxation Relaxation Slide Slide Pearson Education, Inc. Action potential in t-tubule Let s look in a bit more detail alters RyR conformation = about ryanodine receptor-channel of how DHP receptor. calcium gets released from the sarcoplasmic Sarcoplasmic Ca 2+ -ATPase DHP pumps receptor Ca opens RyR Ca reticulum back into SR. 2+ release channels in sarco- Distance actin moves Ca 2+ releases Ca 2+ released ATP Ca 2+ Myosin thick filament KEY DHP = dihydropyridine L-type calcium channel KEY RyR = ryanodine receptor-channel DHP = dihydropyridine L-type calcium channel plasmic reticulum, and Ca 2+ enters Decrease cytoplasm. in free cytosolic [Ca 2+ ] causes Ca 2+ to unbind from troponin. Ca 2+ binds to troponin, allowing actin-myosin binding. Tropomyosin re-covers binding site. When myosin heads Myosin release, heads elastic execute elements power pull filaments back to their relaxed stroke. position. Actin filament slides toward center of sarcomere. AP stops, RyR closes, Ca 2+ return > Ca 2+ release: Muscle relaxes

32 You have decided to move your arm. So, you need to send an efferent signal to your arm from your CNS and make your arm muscle contract. Which ion is most important for triggering muscle contraction during this whole process? A.) K + B.) Na + C.) Ca 2+ D.) Acetylcholine

33 A muscle cell has been depolarized and already is having its action potential. Which ion is most important for triggering muscle contraction after this point? A.) K + B.) Na + C.) Ca 2+ D.) Norepinephrine

34 Some unique and interesting properties of muscle fibers

35 1. Delay between excitation and contraction

36 Figure There s a delay between excitation of the muscle and contraction Action potentials in the axon terminal (top graph) and in the muscle fiber (middle graph) are followed by a muscle twitch (bottom graph). Motor Neuron Action Potential Muscle fiber Action potential from CNS +30 Neuron membrane potential in mv 70 Time Motor end plate Axon terminal Muscle action potential Recording electrodes Muscle Fiber Action Potential +30 Muscle fiber membrane potential in mv N A V I G A T O R 70 2 msec Time Neuromuscular junction (NMJ) Development of Tension During One Muscle Twitch E-C coupling Latent period Contraction phase Relaxation phase Tension Muscle twitch msec FIGURE QUESTIONS Time Movement of what ion(s) in What s causing this what direction(s) delay creates between electrical activity (a) (b) the the neuronal muscle action action potential? potential? and force generation in the muscle?

37 Figure ESSENTIALS Excitation-Contraction Coupling and Relaxation Excitation Contraction Lots of steps in between excitation and contraction leads to ~2-3msec delay

38 2. Energy storage/availability

39 Figure Phosphocreatine Resting muscle stores energy from ATP in the high-energy bonds of phosphocreatine. Working muscle then uses that stored energy. Muscle at rest ATP from metabolism + creatine creatine kinase ADP + phosphocreatine Working muscle Phosphocreatine + ADP creatine kinase Creatine + ATP When these reserves are depleted, ATP is made through aerobic and anaerobic glycolysis. needed for Myosin ATPase (contraction) Ca 2+ -ATPase (relaxation) Na + -K + -ATPase (restores ions that cross cell membrane during action potential to their original compartments)

40 3. Ideal muscle length

41 Figure Adapted from A. M. Gordon et al., J Physiol 184: , LENGTH-TENSION RELATIONSHIPS Too much or too little overlap of thick and thin filaments in resting muscle results in decreased tension. Tension/Force (as percentage of max) A B C 1.3 µ m 2.0 µ m 2.3 µ m 3.7 µ m D E Decreased length Optimal resting length Increased length Sarcomere length

42 4. Motor unit recruitment can help a whole muscle increase force generated

43 Figure MOTOR UNITS A motor unit consists of one motor neuron and all the muscle fibers it innervates. A muscle may have many motor units of different types. One muscle may have many motor units of different fiber types. SPINAL CORD Neuron 1 Neuron 2 Neuron 3 Motor nerve KEY Muscle fibers Motor unit 1 Motor unit 2 Motor unit 3

44

45 How do we get fine motor movement (e.g. hands): only a few muscle fibers per motor unit. Allows for more precise control of movement/fiber activation

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