1. Chapter 8
Muscle Physiology

2. Outline Structure Contractile mechanisms Mechanics Control
Other muscle types
Smooth, cardiac

3. Outline Structure Muscle fiber (from myoblasts) Myofibrils
Thick and thin filaments (actin and myosin)
A,H,M,I,Z
Sarcomere
Titin –elasticity
Cross bridges
Myosin, Actin, tropomyosin, troponin

4. Muscle Comprises largest group of tissues in body
Three types of muscle
Skeletal muscle
Make up muscular system
Cardiac muscle
Found only in the heart
Smooth muscle
Appears throughout the body systems as components of hollow organs and tubes
Classified in two different ways
Striated or unstriated
Voluntary or involuntary

5. Categorization of Muscle

6. Muscle Controlled muscle contraction allows
Purposeful movement of the whole body or parts of the body
Manipulation of external objects
Propulsion of contents through various hollow internal organs
Emptying of contents of certain organs to external environment

7. Structure of Skeletal Muscle
Muscle consists a number of muscle fibers lying parallel to one another and held together by connective tissue
Single skeletal muscle cell is known as a muscle fiber
Multinucleated
Large, elongated, and cylindrically shaped
Fibers usually extend entire length of muscle

8. Muscle Tendon Muscle fiber (a single muscle cell) Connective tissue
Fig. 8-2, p. 255

9. Structure of Skeletal Muscle
Myofibrils
Contractile elements of muscle fiber
Regular arrangement of thick and thin filaments
Thick filaments – myosin (protein)
Thin filaments – actin (protein)
Viewed microscopically myofibril displays alternating dark (the A bands) and light bands (the I bands) giving appearance of striations

10. Muscle
fiber
Dark A band
Light I band
Myofibril
Fig. 8-2, p. 255

11. Structure of Skeletal Muscle
Sarcomere
Functional unit of skeletal muscle
Found between two Z lines (connects thin filaments of two adjoining sarcomeres)
Regions of sarcomere
A band
Made up of thick filaments along with portions of thin filaments that overlap on both ends of thick filaments
H zone
Lighter area within middle of A band where thin filaments do not reach
M line
Extends vertically down middle of A band within center of H zone
I band
Consists of remaining portion of thin filaments that do not project into A band

12. Z line A band I band Portion of myofibril M line H zone Sarcomere
Thick filament
A band
I band
Thin filament
Cross
bridges
M line
H zone
Z line
Myosin
Actin
Thick filament
Thin filament
Fig. 8-2, p. 255

13. I band A band I band Cross bridge Thick filament Thin filament
Fig. 8-4, p. 256

14. Structure of Skeletal Muscle
Titin
Giant, highly elastic protein
Largest protein in body
Extends in both directions from M line along length of thick filament to Z lines at opposite ends of sarcomere
Two important roles:
Along with M-line proteins helps stabilize position of thick filaments in relation to thin filaments
Greatly augments muscle’s elasticity by acting like a spring

15. Myosin Component of thick filament
Protein molecule consisting of two identical subunits shaped somewhat like a golf club
Tail ends are intertwined around each other
Globular heads project out at one end
Tails oriented toward center of filament and globular heads protrude outward at regular intervals
Heads form cross bridges between thick and thin filaments
Cross bridge has two important sites critical to contractile process
An actin-binding site
A myosin ATPase (ATP-splitting) site

16. Structure and Arrangement of Myosin Molecules Within Thick Filament

17. Actin Primary structural component of thin filaments
Spherical in shape
Thin filament also has two other proteins
Tropomyosin and troponin
Each actin molecule has special binding site for attachment with myosin cross bridge
Binding results in contraction of muscle fiber

18. Composition of a Thin Filament

19. Actin and myosin are often called contractile proteins
Actin and myosin are often called contractile proteins. Neither actually contracts.
Actin and myosin are not unique to muscle cells, but are more abundant and more highly organized in muscle cells.

20. Tropomyosin and Troponin
Often called regulatory proteins
Tropomyosin
Thread-like molecules that lie end to end alongside groove of actin spiral
In this position, covers actin sites blocking interaction that leads to muscle contraction
Troponin
Made of three polypeptide units
One binds to tropomyosin
One binds to actin
One can bind with Ca2+

21. Tropomyosin and Troponin
When not bound to Ca2+, troponin stabilizes tropomyosin in blocking position over actin’s cross-bridge binding sites
When Ca2+ binds to troponin, tropomyosin moves away from blocking position
With tropomyosin out of way, actin and myosin bind, interact at cross-bridges
Muscle contraction results

22. Role of Calcium in Cross-Bridge Formation

23. Cross-bridge interaction between actin and myosin brings about muscle contraction by means of the sliding filament mechanism.

24. Outline Contractile mechanisms Sliding filament mechanism (Theory)
Ca dependence
Power stroke
T tubules
Ca release
Lateral sacs, foot proteins, ryanodine receptors, dihydropyradine receptors
Cross bridge cycling
Rigor mortis, relaxation, latent period

25. Sliding Filament Mechanism
Increase in Ca2+ starts filament sliding
Decrease in Ca2+ turns off sliding process
Thin filaments on each side of sarcomere slide inward over stationary thick filaments toward center of A band during contraction
As thin filaments slide inward, they pull Z lines closer together
Sarcomere shortens

26. Basic 4 steps Fig. 8-9, p. 260 Figure 8.9: Cross-bridge activity.
(a) During each cross-bridge cycle, the cross bridge binds with an actin molecule, bends to pull the thin filament inward during the power stroke, then detaches and returns to its resting conformation, ready to repeat the cycle. (b) The power strokes of all cross bridges extending from a thick filament are directed toward the center of the thick filament. (c) Each thick filament is surrounded on each end by six thin filaments, all of which are pulled inward simultaneously through cross-bridge cycling during muscle contraction.
Fig. 8-9, p. 260

27. Hydrolysis of ATP pivots head Release of ADP and Pi cocks head
Detailed steps
Hydrolysis of ATP pivots head
Release of ADP and Pi cocks head
Figure 8.13: Cross-bridge cycle.
Fig. 8-13, p. 263

28. Calcium Release in Excitation-Contraction Coupling

29. Power Stroke
Activated cross bridge bends toward center of thick filament, “rowing” in thin filament to which it is attached
Sarcoplasmic reticulum releases Ca2+ into sarcoplasm
Myosin heads bind to actin
Myosin heads swivel toward center of sarcomere (power stroke)
ATP binds to myosin head and detaches it from actin

30. Power Stroke
Hydrolysis of ATP transfers energy to myosin head and reorients it
Contraction continues if ATP is available and Ca2+ level in sarcoplasm is high

31. Sliding Filament Mechanism
All sarcomeres throughout muscle fiber’s length shorten simultaneously
Contraction is accomplished by thin filaments from opposite sides of each sarcomere sliding closer together between thick filaments

32. Changes in Banding Pattern During Shortening

33. Relaxation
Depends on reuptake of Ca2+ into sarcoplasmic reticulum (SR)
Acetylcholinesterase breaks down ACh at neuromuscular junction
Muscle fiber action potential stops
When local action potential is no longer present, Ca2+ moves back into sarcoplasmic reticulum

34. Terminal button T tubule Acetylcholine- gated cation channel Lateral
Surface membrane of muscle cell
Acetylcholine-
gated cation
channel
Lateral
sacs of
sarcoplasmic
reticulum
Acetylcholine
Troponin
Tropomyosin
Actin
Cross-bridge binding
Myosin cross bridge
Fig. 8-12, p. 262

35. T Tubules and Sarcoplasmic Reticulum

36. Sarcoplasmic Reticulum
Modified endoplasmic reticulum
Consists of fine network of interconnected compartments that surround each myofibril
Not continuous but encircles myofibril throughout its length
Segments are wrapped around each A band and each I band
Ends of segments expand to form saclike regions – lateral sacs (terminal cisternae)

37. Transverse Tubules T tubules
Run perpendicularly from surface of muscle cell membrane into central portions of the muscle fiber
Since membrane is continuous with surface membrane – action potential on surface membrane also spreads down into T-tubule
Spread of action potential down a T tubule triggers release of Ca2+ from sarcoplasmic reticulum into cytosol

38. Relationship Between T Tubule and Adjacent Lateral Sacs of Sarcoplasmic Reticulum

39. Outline Mechanics Tendons Twitch Motor unit Motor unit recruitment
Fatigue
Asynchronous recruitment
Twitch, tetanus, summation
Muscle length, isometric, isotonic
Tension, origin, insertion

40. Skeletal Muscle Mechanics
Muscle consists of groups of muscle fibers bundled together and attached to bones
Connective tissue covering muscle divides muscle internally into bundles
Connective tissue extends beyond ends of muscle to form tendons
Tendons attach muscle to bone

41. Muscle Contractions
Contractions of whole muscle can be of varying strength
Twitch
Brief, weak contraction
Produced from single action potential
Too short and too weak to be useful
Normally does not take place in body
Two primary factors which can be adjusted to accomplish gradation of whole-muscle tension
Number of muscle fibers contracting within a muscle
Tension developed by each contracting fiber

42. Motor Unit Recruitment
One motor neuron and the muscle fibers it innervates
Number of muscle fibers varies among different motor units
Number of muscle fibers per motor unit and number of motor units per muscle vary widely
Muscles that produce precise, delicate movements contain fewer fibers per motor unit
Muscles performing powerful, coarsely controlled movement have larger number of fibers per motor unit

43. Motor Unit Recruitment
Asynchronous recruitment of motor units helps delay or prevent fatigue
Factors influencing extent to which tension can be developed
Frequency of stimulation
Length of fiber at onset of contraction
Extent of fatigue
Thickness of fiber

44. Schematic Representation of Motor Units in Skeletal Muscle

45. Twitch Summation and Tetanus
Results from sustained elevation of cytosolic calcium
Tetanus
Occurs if muscle fiber is stimulated so rapidly that it does not have a chance to relax between stimuli
Contraction is usually three to four times stronger than a single twitch

46. Summation and Tetanus

47. Muscle Tension Tension is produced internally within sarcomeres
Tension must be transmitted to bone by means of connective tissue and tendons before bone can be moved (series-elastic component)
Muscle typically attached to at least two different bones across a joint
Origin
End of muscle attached to more stationary part of skeleton
Insertion
End of muscle attached to skeletal part that moves

48. Fig. 8-17, p. 268 Figure 8.17: Length–tension relationship.
Maximal tetanic contraction can be achieved when a muscle fiber is at its optimal length (lo) before the onset of contraction, because this is the point of optimal overlap of thick-filament cross bridges and thin-filament cross-bridge binding sites (point A). The percentage of maximal tetanic contraction that can be achieved decreases when the muscle fiber is longer or shorter than lo before contraction. When it is longer, fewer thin-filament binding sites are accessible for binding with thick-filament cross bridges, because the thin filaments are pulled out from between the thick filaments (points B and C). When the fiber is shorter, fewer thin-filament binding sites are exposed to thick-filament cross bridges because the thin filaments overlap (point D). Also, further shortening and tension development are impeded as the thick filaments become forced against the Z lines (point D). In the body, the resting muscle length is at lo. Furthermore, because of restrictions imposed by skeletal attachments, muscles cannot vary beyond 30% of their lo in either direction (the range screened in light green). At the outer limits of this range, muscles still can achieve about 50% of their maximal tetanic contraction.
Fig. 8-17, p. 268

49. Types of Contraction Two primary types Isotonic Isometric
Muscle tension remains constant as muscle changes length
Isometric
Muscle is prevented from shortening
Tension develops at constant muscle length

50. Contraction-Relaxation Steps Requiring ATP
Splitting of ATP by myosin ATPase provides energy for power stroke of cross bridge
Binding of fresh molecule of ATP to myosin lets bridge detach from actin filament at end of power stroke so cycle can be repeated
Active transport of Ca2+ back into sarcoplasmic reticulum during relaxation depends on energy derived from breakdown of ATP

51. Energy Sources for Contraction
Transfer of high-energy phosphate from creatine phosphate to ADP
First energy storehouse tapped at onset of contractile activity
Oxidative phosphorylation (citric acid cycle and electron transport system
Takes place within muscle mitochondria if sufficient O2 is present
Glycolysis
Supports anaerobic or high-intensity exercise

52. Muscle Fatigue
Occurs when exercising muscle can no longer respond to stimulation with same degree of contractile activity
Defense mechanism that protects muscle from reaching point at which it can no longer produce ATP
Underlying causes of muscle fatigue are unclear

53. Central Fatigue
Occurs when CNS no longer adequately activates motor neurons supplying working muscles
Often psychologically based
Mechanisms involved in central fatigue are poorly understood

54. Outline Other types Fibers Smooth, cardiac Creatine phosphate
Fast
slow
Oxidative
glycolytic
Smooth, cardiac
Creatine phosphate
Oxidative phosphorulation
Aerobic, myoglobin
Glycolysis
Anaerobic, lactic acid

55. Major Types of Muscle Fibers
Classified based on differences in ATP hydrolysis and synthesis
Three major types
Slow-oxidative (type I) fibers
Fast-oxidative (type IIa) fibers
Fast-glycolytic (type IIx) fibers

56. Characteristics of Skeletal Muscle Fibers

57. Control of Motor Movement
Three levels of input control motor-neuron output
Input from afferent neurons
Input from primary motor cortex
Input from brain stem

58. Muscle Spindle Structure
Consist of collections of specialized muscle fibers known as intrafusal fibers
Lie within spindle-shaped connective tissue capsules parallel to extrafusal fibers
Each spindle has its own private efferent and afferent nerve supply
Play key role in stretch reflex

59. Muscle Spindle Function

60. Contractile end portions of intrafusal fiber
Capsule
Alpha motor
neuron axon
Intrafusal (spindle)
muscle fibers
Gamma motor
neuron axon
Contractile end portions
of intrafusal fiber
Noncontractile
central portion
of intrafusal
fiber
Secondary (flower-spray)
endings of afferent
fibers
Primary (annulospiral)
endings of afferent fibers
Extrafusal (“ordinary”)
muscle fibers
Fig. 8-24, p. 283

61. Stretch Reflex
Primary purpose is to resist tendency for passive stretch of extensor muscles by gravitational forces when person is standing upright
Classic example is patellar tendon, or knee-jerk reflex

62. Patellar Tendon Reflex

63. Outline Other muscle types Smooth, cardiac
This information is covered in detail in the lecture on the heart.

64. Smooth Muscle Found in walls of hollow organs and tubes No striations
Filaments do not form myofibrils
Not arranged in sarcomere pattern found in skeletal muscle
Spindle-shaped cells with single nucleus
Cells usually arranged in sheets within muscle
Have dense bodies containing same protein found in Z lines

65. Smooth Muscle Cell has three types of filaments Thick myosin filaments
Longer than those in skeletal muscle
Thin actin filaments
Contain tropomyosin but lack troponin
Filaments of intermediate size
Do not directly participate in contraction
Form part of cytoskeletal framework that supports cell shape

66. Intermediate filament Thick filament Thin filament Dense body
Stepped art
Fig. 8-28, p. 288

67. Calcium Activation of Myosin Cross Bridge in Smooth Muscle

68. Comparison of Role of Calcium In Bringing About Contraction in Smooth Muscle and Skeletal Muscle

69. Smooth Muscle Two major types Multiunit smooth muscle
Single-unit smooth muscle

70. Multiunit Smooth Muscle
Neurogenic
Consists of discrete units that function independently of one another
Units must be separately stimulated by nerves to contract
Found
In walls of large blood vessels
In large airways to lungs
In muscle of eye that adjusts lens for near or far vision
In iris of eye
At base of hair follicles

71. Single-unit Smooth Muscle
Self-excitable (does not require nervous stimulation for contraction)
Also called visceral smooth muscle
Fibers become excited and contract as single unit
Cells electrically linked by gap junctions
Can also be described as a functional syncytium
Contraction is slow and energy-efficient
Well suited for forming walls of distensible, hollow organs

72. Cardiac Muscle Found only in walls of heart Striated
Cells are interconnected by gap junctions
Fibers are joined in branching network
Innervated by autonomic nervous system