1. Muscle Physiology

2. Muscle Tissue
Muscle accounts for nearly half of the body’s mass - Muscles have the ability to change chemical energy (ATP) into mechanical energy
Three types of Muscle Tissue – differ in structure, location, function, and means of activation
Skeletal Muscle
Cardiac Muscle
Smooth Muscle

3. Skeletal Muscle Skeletal muscles attach to and cover the bony skeleton
Is controlled voluntarily (i.e., by conscious control)
Contracts rapidly but tires easily
Is responsible for overall body motility
Is extremely adaptable and can exert forces ranging from a fraction of an ounce to over 70 pounds
Has obvious stripes called striations
Each muscle cell is multinucleated

4. Microscopic Anatomy - Skeletal Muscle Fiber
Sarcoplasm contains glycosomes (granules of glycogen) and the oxygen-binding protein called myoglobin
In addition to the typical organelles, fibers have
Sarcoplasmic reticulum
T tubules - modifications of the sarcolemma
Myofibrils
Each muscle fiber is made of many myofibrils, 80% of the muscle volume, that contain the contractile elements of skeletal muscle cells

5. Myofibrils - Striations
Myofibrils are made up of 2 types of contractile proteins called myofilaments
Thick (Myosin) filaments
Thin (Actin) filaments
The arrangement of myofibrils creates a series of repeating dark A (anisotropic) bands and light I (isotropic) bands

6. Myofibrils - Striations
The A band has a light stripe in the center called the H (helle) zone
The H zone is bisected by a dark line, the M line
I band has a darker midline called the Z disc (or Z line)

7. Sarcomere Smallest contractile unit of a muscle
Myofibril region between two successive Z discs, has a central A band and partial (half) I bands at each end

8. Thick Filaments (16 nm diam) Myosin
Each myosin molecule (two interwoven polypeptide chains) has a rodlike tail and two globular heads
During muscle contraction, the Heads link the thick and thin filaments together, forming cross bridges

9. Thin Filaments - Actin
Thin filaments are mostly composed of the protein actin.
Provides active sites where myosin heads attach during contraction. Tropomyosin and Troponin are regulatory subunits bound to actin.

10. Ultrastructure of Muscle
Myofibril
A band
Z disk
I band
M line
H zone
Sarcomere
Thin filaments
Tropomyosin
Troponin
Actin chain
G-actin molecule
Myosin tail
Myosin
heads
Myosin molecule
(c)
(d)
(e)
Thick filaments
Hinge
region
(f)
Titin
Nebulin
Figure 12-3c–f

11. Arrangement of Filaments in a Sarcomere

12. Sarcoplasmic Reticulum (SR)
SR - an elaborate, smooth ER that surrounds each myofibril. Perpendicular (transverse) channels at the A band - I band junction are the Terminal Cisternae (Lateral Sacs) SR regulates intracellular Ca2+
T tubules at each A band/I band junction - continuous with the sarcolemma. Conduct electrical impulses to the throughout cell (every sarcomere) - signals for the release of Ca2+ from adjacent terminal cisternae

13. Triad – 2 terminal cisternae and 1 T tubule
T tubules and SR provide tightly linked signals for muscle contraction
Interaction of integral membrane proteins (IMPs) from T tubules and SR

14. Interaction of T-Tubule Proteins and SR Foot Proteins
T tubule proteins (Dihydropyridine) act as voltage sensors
SR foot proteins are (ryanodine) receptors that regulate Ca2+ release from the SR cisternae
Action potential in t-tubule alters conformation of DHP receptor
DHP receptor opens Ca2+ release channels in sarcoplasmic reticulum and Ca2+ enters cytoplasm
Ca2+
released
(b)
DHP receptor
SR Foot Protein (Ca++ release channel)

15. Sliding Filament Model of Contraction
Contraction refers to the activation of myosin’s cross bridges – the sites that generate the force
In the relaxed state, actin and myosin filaments do not fully overlap
With stimulation by the nervous system, myosin heads bind to actin and pull the thin filaments
Actin filaments slide past the myosin filaments so that the actin and myosin filaments overlap to a greater degree (the actin filaments are moved toward the center of the sarcomere, Z lines become closer)

16. Sliding Filament Model of Contraction

17. Sliding Filament Model of Contraction

18. Skeletal Muscle Contraction
For contraction to occur, a skeletal muscle must:
Be stimulated by a nerve ending
Propagate an electrical current, or action potential, along its sarcolemma
Have a rise in intracellular Ca2+ levels, the final stimulus for contraction
The series of events linking the action potential to contraction is called excitation-contraction coupling

19. Depolarization and Generation of an AP
The sarcolemma, like other plasma membranes is polarized. There is a potential difference (voltage) across the membrane
When Ach binds to its receptors on the motor end plate, chemically (ligand) gated ion channels in the receptors open and allow Na+ and K+ to move across the membrane, resulting in a transient change in membrane potential - Depolarization
End plate potential - a local depolarization that creates and spreads an action potential across the sarcolemma

20. Excitation-Contraction Coupling
E-C Coupling is the sequence of events linking the transmission of an action potential along the sarcolemma to muscle contraction (the sliding of myofilaments)
The action potential lasts only 1-2 ms and ends before contraction occurs.
The period between action potential initiation and the beginning of contraction is called the latent period.
E-C coupling occurs within the latent period.

21. Regulatory Role of Tropomyosin and TroponinPi
ADP
G-actin moves
Cytosolic Ca2+
Tropomyosin shifts,
exposing binding
site on G-actin TN
Power stroke
Initiation of contraction
Ca2+ levels increase
in cytosol.
Ca2+ binds to
troponin.
Troponin-Ca2+
complex pulls
tropomyosin
away from G-actin
binding site.
Myosin binds
to actin and
completes power
stroke.
Actin filament
moves.
(b) 1 2 3 4 5
Figure 12-10b, steps 1–5

22. Excitation-Contraction Coupling
Muscle fiber
Motor end plate
ACh
Axon terminal of
somatic motor neuron
Sarcoplasmic reticulum
Actin
Troponin
Tropomyosin
Myosin
head
Z disk
Myosin thick filament
M line
T-tubule
DHP
receptor
Ca2+
Somatic motor neuron
releases ACh at neuro-
muscular junction.
Net entry of Na+ through ACh
receptor-channel initiates
a muscle action potential.
Na+ K+
(a)
potential 1
Action 2
Action potential
Figure 12-11a, steps 1–2

23. Excitation-Contraction Coupling
The action potential is propagated along (across) the sarcolemma and travels through the T tubules
At the triads, the action potential causes voltage sensitive T tubule proteins to change shape. This change, in turn, causes the SR foot proteins of the terminal cisternae to change shape, Ca2+ channels are opened and Ca2+ is released into the sarcoplasm (where the myofilaments are)
Terminal button
Acetylcholine-
gated cation
channel
Acetylcholine
T tubule
Surface membrane of muscle cell
Tropomyosin
Troponin
Cross-bridge binding
Myosin cross bridge
Actin

24. Excitation-Contraction Coupling
Some of the Ca2+ binds to troponin, troponin changes shape and causes tropomysin to move which exposes the active binding sites on actin
Myosin heads can now alternately attach and detach, pulling the actin filaments toward the center of the sarcomere (ATP hydrolysis is necessary)

25. Excitation-Contraction Coupling
The short calcium influx ends (30 ms after the action potential ends) and Ca2+ levels fall. An ATP-dependent Ca2+ pump is continually moving Ca2+ back into the SR.
Tropomyosin blockage of the actin binding sites is reestablished as Ca2+ levels drop. Cross bridge activity ends and relaxation occurs

26. The Molecular Basis of Contraction
At the end of the power stroke,
the myosin head releases ADP
and resumes the tightly bound
rigor state.
ATP
binding
site
Myosin
sites
ADP
Tight binding in the rigor
state. The crossbridge is
at a 45° angle relative to
the filaments.
Myosin filament
45°
G-actin molecule
ATP binds to its binding site
on the myosin. Myosin then
dissociates from actin.
The ATPase activity of myosin
hydrolyzes the ATP. ADP and
Pi remain bound to myosin.
The myosin head swings over and
binds weakly to a new actin molecule.
The crossbridge is now at 90º relative
to the filaments. Pi
90°
Release of Pi initiates the power
stroke. The myosin head rotates
on its hinge, pushing the actin
filament past it.
Actin filament
moves toward M line.
Contraction-
relaxation
Sliding
filament 1 2 3 4 5 6
Figure 12-9

27. Sequential Events of Contraction

28. Motor Unit
Motor unit - 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

29. Electrical and Mechanical Events in Muscle Contraction
A twitch is a single contraction-relaxation cycle
Figure 12-12

30. Muscle Twitch
A muscle twitch is the response of the muscle fibers of a motor unit to a single action potential of its motor neuron. The fibers contract quickly and then relax. Three Phases:
Latent Period – the first few ms after stimulation when excitation-contraction is occurring
Period of Contraction – cross bridges are active and the muscle shortens if the tension is great enough to overcome the load
Period of Relaxation – Ca2+ is pumped back into SR and muscle tension decreases to baseline level

31. Graded Muscle Responses
Graded muscle responses are:
Variations in the degree or strength of muscle contraction in response to demand
Required for proper control of skeletal movement
Muscle contraction can be graded (varied) in two ways:
Changing the frequency of the stimulus
Changing the strength of the stimulus

32. Muscle Response to Stimulation Frequency
A single stimulus results in a single contractile response – a muscle twitch (contracts and relaxes)
More frequent stimuli increases contractile force – wave summation - muscle is already partially contracted when next stimulus arrives and contractions are summed

33. Muscle Response to Stimulation Frequency
More rapidly delivered stimuli result in incomplete tetanus – sustained but quivering contraction
If stimuli are given quickly enough, complete tetanus results – smooth, sustained contraction with no relaxation period

34. Summation and Tetanus

35. Factors Affecting Force of Muscle Contraction
Number of motor units recruited, recruitment also helps provide smooth muscle action rather than jerky movements
The relative size of the muscle fibers – the bulkier the muscle fiber (greater cross-sectional area), the greater its strength
Asynchronous recruitment of motor units -while some motor units are active others are inactive - this pattern of firing provides a brief rest for the inactive units preventing fatigue
Degree of muscle stretch

36. Length – Tension Relationship
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.

37. Muscle Tone The constant, slightly contracted state of all muscles
Does not produce active movements
Keeps the muscles firm and ready to respond to stimulus
Helps stabilize joints and maintain posture
Due to spinal reflex activation of motor units in response to stretch receptors in muscles and tendons

38. Contraction of Skeletal Muscle Fibers
The force exerted on an object by a contracting muscle is called muscle tension, the opposing force or weight of the object to be moved is called the load.
Two types of Muscle Contraction:
When muscle tension develops, but the load is not moved (muscle does not shorten) the contraction is called Isometric
If muscle tension overcomes (moves) the load and the muscle shortens, the contraction is called Isotonic

39. Isometric Contractions
No change in overall muscle length
In isometric contractions, increasing muscle tension (force) is measured

40. Isotonic Contraction
In isotonic contractions, the muscle changes length and moves the load. Once sufficient tension has developed to move the load, the tension remains relatively constant through the rest of the contractile period.
Two types of isotonic contractions:
Concentric contractions – the muscle shortens and does work
Eccentric contractions – the muscle contracts as it lengthens

41. Isotonic Contraction
This illustrates a concentric isotonic contraction
In isotonic contractions, the amount of shortening (distance in mm) is measured

42. Energy Sources for Contraction
ATP is the only energy source that is used directly for contractile activity
As soon as available ATP is hydrolyzed (4-6 seconds), it is regenerated by three pathways:
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

43. CP-ADP Reaction
Transfer of energy as a phosphate group is moved from CP to ADP – the reaction is catalyzed by the enzyme creatine kinase
Creatine phosphate + ADP → creatine + ATP
Stored ATP and CP provide energy for maximum muscle power for seconds

44. Anaerobic Glycolysis
Glucose is broken down into pyruvic acide to yield 2 ATP
When oxygen demand cannot be met, pyruvic acid is converted into lactic acid
Lactic acid diffuses into the bloodstream – can be used as energy source by the liver, kidneys, and heart
Can be converted back into pyruvic acid, glucose, or glycogen by the liver

45. Glycolysis and Aerobic Respiration
Aerobic respiration occurs in mitochondria - requires O2
A series of reactions breaks down glucose for high yield of ATP
Glucose + O2 → CO2 + H2O + ATP

46. Muscle Fatigue
Muscle fatigue – the muscle is physiologically not able to contract
Occurs when oxygen is limited and ATP production fails to keep pace with ATP use
Lactic acid accumulation and ionic imbalances may also contribute to muscle fatigue
Depletion of energy stores – glycogen
When no ATP is available, contractures (continuous contraction) may result because cross bridges are unable to detach

47. Muscle Fiber Type: Speed of Contraction
Speed of contraction – determined by how fast their myosin ATPases split ATP
Oxidative fibers – use aerobic pathways
Glycolytic fibers – use anaerobic glycolysis
Based on these two criteria skeletal muscles may be classified as:
Slow oxidative fibers (Type I) - contract slowly, have slow acting myosin ATPases, and are fatigue resistant
Fast oxidative fibers (Type IIA)- contract quickly, have fast myosin ATPases, and have moderate resistance to fatigue
Fast glycolytic fibers (Type IIB)- contract quickly, have fast myosin ATPases, and are easily fatigued

48. Smooth Muscle Occurs within most organs
Walls of hollow visceral organs, such as the stomach
Urinary bladder
Respiratory passages
Arteries and veins
Helps substances move through internal body channels via peristalsis
No striations
Filaments do not form myofibrils
Not arranged in sarcomere pattern found in skeletal muscle
Is Involuntary
Single Nucleus

49. Smooth Muscle
Composed of spindle-shaped fibers with a diameter of 2-10 m and lengths of several hundred m
Cells usually arranged in sheets within muscle
Organized into two layers (longitudinal and circular) of closely apposed fibers
Have essentially the same contractile mechanisms as skeletal muscle

50. 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
Have dense bodies containing same protein found in Z lines

51. Contraction of Smooth Muscle
Whole sheets of smooth muscle exhibit slow, synchronized contraction
Smooth muscle lacks neuromuscular junctions
Action potentials are transmitted from cell to cell
Some smooth muscle cells:
Act as pacemakers and set the contractile pace for whole sheets of muscle
Are self-excitatory and depolarize without external stimuli
Stimuli Influencing Smooth Muscle Contractile Activity

52. Smooth Muscle Muscle fiber stimulated
Ca2+ released into the cytoplasm from ECF
Ca2+ binds with calmodulin
Ca2+/Calmodulin activates mysoin kinase
Myosin kinase phosphorylates myosin
Myosin can now bind with actin

53. Smooth Muscle Contraction
ECF
Ca2+
Sarcoplasmic
reticulum
CaM Pi
Active
MLCK
ADP +
Active myosin
ATPase
Actin P
Intracellular Ca2+
concentrations increase
when Ca2+ enters cell
and is released from
sarcoplasmic reticulum.
Ca2+ binds to
calmodulin (CaM).
Ca2+–calmodulin
activates myosin light
chain kinase (MLCK).
MLCK phosphorylates
light chains in myosin
heads and increases
myosin ATPase activity.
crossbridges slide
along actin and create
muscle tension.
ATP
Increased
muscle
tension
Inactive myosin
Inactive 1 2 3 4 5
Figure 12-28, steps 1–5

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

55. Cardiac Muscle Tissue Occurs only in the heart
Is striated like skeletal muscle but but has a branching pattern with intercalated Discs
Usually one nucleus, but may have more
Is not voluntary
Contracts at a fairly steady rate set by the heart’s pacemaker
Neural controls allow the heart to respond to changes in bodily needs