1. Highlights of Muscle Physiology From Marieb

2. Events at the Neuromuscular Junction

3. Figure 9.8 Nucleus Action potential (AP) Myelinated axon of motor neuron Axon terminal of neuromuscular junction Sarcolemma of the muscle fiber Ca 2+ Axon terminal of motor neuron Synaptic vesicle containing ACh Mitochondrion Synaptic cleft Junctional folds of sarcolemma Fusing synaptic vesicles ACh Sarcoplasm of muscle fiber Postsynaptic membrane ion channel opens; ions pass. Na + K+K+ Ach – Na + K+K+ Degraded ACh Acetyl- cholinesterase Postsynaptic membrane ion channel closed; ions cannot pass. 1 Action potential arrives at axon terminal of motor neuron. 2 Voltage-gated Ca 2+ channels open and Ca 2+ enters the axon terminal. 3 Ca 2+ entry causes some synaptic vesicles to release their contents (acetylcholine) by exocytosis. 4 Acetylcholine, a neurotransmitter, diffuses across the synaptic cleft and binds to receptors in the sarcolemma. 5 ACh binding opens ion channels that allow simultaneous passage of Na + into the muscle fiber and K + out of the muscle fiber. 6 ACh effects are terminated by its enzymatic breakdown in the synaptic cleft by acetylcholinesterase.

4. Events in Generation of an Action Potential

5. Figure 9.9 Na + Open Na + Channel Closed Na + Channel Closed K + Channel Open K + Channel Action potential + + ++ + + + + ++ + + Axon terminal Synaptic cleft ACh Sarcoplasm of muscle fiber K+K+ 2 Generation and propagation of the action potential (AP) 3 Repolarization 1 Local depolarization: generation of the end plate potential on the sarcolemma K+K+ K+K+ Na + K+K+ W a v e o f d e p o l a r i z a t i o n

6. Figure 9.9, step 1 Na + Open Na + Channel Closed K + Channel K+K+ Na + K+K+ Action potential + + + + + + + + + + + + Axon terminal Synaptic cleft ACh Sarcoplasm of muscle fiber K+K+ 1 Local depolarization: generation of the end plate potential on the sarcolemma 1 W a v e o f d e p o l a r i z a t i o n

7. Figure 9.9, step 2 Na + Open Na + Channel Closed K + Channel K+K+ Na + K+K+ Action potential + + + + + + + + + + + + Axon terminal Synaptic cleft ACh Sarcoplasm of muscle fiber K+K+ Generation and propagation of the action potential (AP) 1 Local depolarization: generation of the end plate potential on the sarcolemma 2 1 W a v e o f d e p o l a r i z a t i o n

8. Figure 9.9, step 3 Na + Closed Na + Channel Open K + Channel K+K+ Repolarization 3

9. Figure 9.9 Na + Open Na + Channel Closed K + Channel Action potential + + ++ + + + + ++ + + Axon terminal Synaptic cleft ACh Sarcoplasm of muscle fiber K+K+ 2 Generation and propagation of the action potential (AP) 3 Repolarization 1 Local depolarization: generation of the end plate potential on the sarcolemma K+K+ K+K+ Na + K+K+ W a v e o f d e p o l a r i z a t i o n Closed Na + Channel Open K + Channel

10. Excitation-Contraction Coupling You demonstrated this in lab with your sarcomere models.

11. Figure 9.11, step 1 Axon terminal of motor neuron Muscle fiber Triad One sarcomere Synaptic cleft Setting the stage Sarcolemma Action potential is generated Terminal cisterna of SR ACh Ca 2+

12. Figure 9.11, step 2 Action potential is propagated along the sarcolemma and down the T tubules. Steps in E-C Coupling: Troponin Tropomyosin blocking active sites Myosin Actin Active sites exposed and ready for myosin binding Ca 2+ Terminal cisterna of SR Voltage-sensitive tubule protein T tubule Ca 2+ release channel Myosin cross bridge Ca 2+ Sarcolemma Calcium ions are released. Calcium binds to troponin and removes the blocking action of tropomyosin. Contraction begins The aftermath 1 2 3 4

13. Figure 9.11, step 3 Steps in E-C Coupling: Terminal cisterna of SR Voltage-sensitive tubule protein T tubule Ca 2+ release channel Ca 2+ Sarcolemma Action potential is propagated along the sarcolemma and down the T tubules. 1

14. Figure 9.11, step 4 Steps in E-C Coupling: Terminal cisterna of SR Voltage-sensitive tubule protein T tubule Ca 2+ release channel Ca 2+ Sarcolemma Action potential is propagated along the sarcolemma and down the T tubules. Calcium ions are released. 1 2

15. Figure 9.11, step 5 TroponinTropomyosin blocking active sites Myosin Actin Ca 2+ The aftermath

16. Figure 9.11, step 6 TroponinTropomyosin blocking active sites Myosin Actin Active sites exposed and ready for myosin binding Ca 2+ Calcium binds to troponin and removes the blocking action of tropomyosin. The aftermath 3

17. Figure 9.11, step 7 TroponinTropomyosin blocking active sites Myosin Actin Active sites exposed and ready for myosin binding Ca 2+ Myosin cross bridge Calcium binds to troponin and removes the blocking action of tropomyosin. Contraction begins The aftermath 3 4

18. Figure 9.11, step 8 Action potential is propagated along the sarcolemma and down the T tubules. Steps in E-C Coupling: Troponin Tropomyosin blocking active sites Myosin Actin Active sites exposed and ready for myosin binding Ca 2+ Terminal cisterna of SR Voltage-sensitive tubule protein T tubule Ca 2+ release channel Myosin cross bridge Ca 2+ Sarcolemma Calcium ions are released. Calcium binds to troponin and removes the blocking action of tropomyosin. Contraction begins The aftermath 1 2 3 4

19. Figure 9.12 1 Actin Cross bridge formation. Cocking of myosin head. The power (working) stroke. Cross bridge detachment. Ca 2+ Myosin cross bridge Thick filament Thin filament ADP Myosin PiPi ATP hydrolysis ATP 24 3 ADP PiPi PiPi

20. Figure 9.12 1 Actin Cross bridge formation. Cocking of myosin head. The power (working) stroke. Cross bridge detachment. Ca 2+ Myosin cross bridge Thick filament Thin filament ADP Myosin PiPi ATP hydrolysis ATP 24 3 ADP PiPi PiPi

21. Muscle Mechanics You studied these concepts in the Physio Ex simulation.

22. Muscle Twitch Response of a muscle to a single, brief threshold stimulus Simplest contraction observable in the lab (recorded as a myogram)

23. Figure 9.14a Latent period Single stimulus Period of contraction Period of relaxation (a) Myogram showing the three phases of an isometric twitch

24. Figure 9.14b Latent period Extraocular muscle (lateral rectus) Gastrocnemius Soleus Single stimulus (b) Comparison of the relative duration of twitch responses of three muscles

25. Graded Muscle Responses Variations in the degree of muscle contraction Required for proper control of skeletal movement Responses are graded by: 1.Changing the frequency of stimulation 2.Changing the strength of the stimulus

26. Response to Change in Stimulus Frequency Increase frequency of stimulus (muscle does not have time to completely relax between stimuli) Ca 2+ release stimulates further contraction  temporal (wave) summation Further increase in stimulus frequency  unfused (incomplete) tetanus

27. Figure 9.15b Stimuli Partial relaxation Low stimulation frequency unfused (incomplete) tetanus (b) If another stimulus is applied before the muscle relaxes completely, then more tension results. This is temporal (or wave) summation and results in unfused (or incomplete) tetanus.

28. Figure 9.15c Stimuli High stimulation frequency fused (complete) tetanus (c) At higher stimulus frequencies, there is no relaxation at all between stimuli. This is fused (complete) tetanus.

29. Response to Change in Stimulus Strength Threshold stimulus: stimulus strength at which the first observable muscle contraction occurs Muscle contracts more vigorously as stimulus strength is increased above threshold Contraction force is precisely controlled by recruitment (multiple motor unit summation), which brings more and more muscle fibers into action

30. Muscle Tone Constant, slightly contracted state of all muscles Due to spinal reflexes that activate groups of motor units alternately in response to input from stretch receptors in muscles Keeps muscles firm, healthy, and ready to respond

31. Muscle Metabolism: Energy for Contraction…Important ATP is regenerated by: – Direct phosphorylation of ADP by creatine phosphate (CP) – Anaerobic pathway (glycolysis) – Aerobic respiration

32. Figure 9.20 Short-duration exercise Prolonged-duration exercise ATP stored in muscles is used first. ATP is formed from creatine Phosphate and ADP. Glycogen stored in muscles is broken down to glucose, which is oxidized to generate ATP. ATP is generated by breakdown of several nutrient energy fuels by aerobic pathway. This pathway uses oxygen released from myoglobin or delivered in the blood by hemoglobin. When it ends, the oxygen deficit is paid back.

33. Muscle Fatigue Physiological inability to contract Occurs when: – Ionic imbalances (K +, Ca 2+, P i ) interfere with E-C coupling – Prolonged exercise damages the SR and interferes with Ca 2+ regulation and release Total lack of ATP occurs rarely, during states of continuous contraction, and causes contractures (continuous contractions)

34. What determines the force of muscle contraction?

35. Figure 9.21 Large number of muscle fibers activated Contractile force High frequency of stimulation Large muscle fibers Muscle and sarcomere stretched to slightly over 100% of resting length

36. Velocity and Duration of Contraction Influenced by: 1.Muscle fiber type 2.Load 3.Recruitment

37. Table 9.2

38. Figure 9.23 Predominance of fast glycolytic (fatigable) fibers Predominance of slow oxidative (fatigue-resistant) fibers Small load Contractile velocity Contractile duration

39. Figure 9.25 Stimulus Intermediate load Light load Heavy load (a) The greater the load, the less the muscle shortens and the shorter the duration of contraction (b) The greater the load, the slower the contraction

40. Effects of Exercise Aerobic (endurance) exercise: Leads to increased: – Muscle capillaries – Number of mitochondria – Myoglobin synthesis Results in greater endurance, strength, and resistance to fatigue May convert fast glycolytic fibers into fast oxidative fibers

41. Effects of Resistance Exercise Resistance exercise (typically anaerobic) results in: – Muscle hypertrophy (due to increase in fiber size) – Increased mitochondria, myofilaments, glycogen stores, and connective tissue

42. Contraction of Smooth Muscle Slow, synchronized contractions Cells are electrically coupled by gap junctions Some cells are self-excitatory (depolarize without external stimuli); act as pacemakers for sheets of muscle Rate and intensity of contraction may be modified by neural and chemical stimuli

43. Contraction of Smooth Muscle Very energy efficient (slow ATPases) Myofilaments may maintain a latch state for prolonged contractions Relaxation requires: Ca 2+ detachment from calmodulin Active transport of Ca 2+ into SR and ECF Dephosphorylation of myosin to reduce myosin ATPase activity

44. Regulation of Contraction Neural regulation: Neurotransmitter binding   [Ca 2+ ] in sarcoplasm; either graded (local) potential or action potential Response depends on neurotransmitter released and type of receptor molecules

45. Table 9.3

46. Types of Smooth Muscle Single-unit (visceral) smooth muscle: – Sheets contract rhythmically as a unit (gap junctions) – Often exhibit spontaneous action potentials – Arranged in opposing sheets and exhibit stress- relaxation response

47. Types of Smooth Muscle: Multiunit Multiunit smooth muscle: – Located in large airways, large arteries, arrector pili muscles, and iris of eye – Gap junctions are rare – Arranged in motor units – Graded contractions occur in response to neural stimuli