Skeletal Muscle Physiology Basics

1. SKELETAL MUSCLE
Dr Ahmad Saleem

2. Skeletal Muscle Fibre
• 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
– Functional Unit of Skeletal Muscle
– Length varies from few mm to many cm.
– Diameter of 10 to 100 micron
– Multinucleated
– Large, elongated, and cylindrically shaped
– Fibers usually extend entire length of muscle
– Like other cells , MF contains motochondria,
microsomes and endoplasmic reticulum etc

3. • Each Muscle Fiber is surrounded by a plasma
membrane called SARCOLEMMA.
• Individual MF is enveloped by layer of connective
tissue called ENDOMYSIUM ( which lies outside
Sarcolemma)
• Several MF are enveloped together by another
connective tissue called PERIMYSIUM
• The entire Muscle is covered all round by
EPIMYSIUM.
( Sarcolemma—Endomysium– Perimysium– Epimysium)

4. • Actin forms the major part of thin filaments.
– The thin filaments give rise to I- bands
– Actin occurs in two forms
• G-Actin ( Globular monomer)
– Each molecule contains one molecule of ATP
– Molecular weight of about 43000.
• F-Actin ( Globular monomer)
– Fibrous, thickness of 6-7 nm, polymerized G-Actin,
contains ADP.
– Polymerization occurs in presence of Calcium or
Magnesium ions.

5. • Myosin –II
– Found in Thick Filaments
– Mol Weight of about 460,000.
– Chief Actin Binding Constituent.
– Hexamer containing two identical heavy chains
and 4 light chains.

6. • Troponin
– Troponin –C
– Can bind an release Calcium Ions.
– Troponin-I
– Exerts an inhibitory action over Actin-Myocin interaction
when Troponin C is without Calcium.
– Troponin T
– Serves to bind Troponin C and Troponin I subunits with
Tropomyosin-Actin Complex.
(Troponin complex is found only in Striated Muscle)

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

8. 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
– Light bands , Only Actin, Isotropic to polarized light-thus
I-Bands.
– Dark bands, Mainly myosin, Anisotropic to polarized
light-Thus A-Bands

9. Muscle
fiber
Dark A band Light I band
Myofibril
Fig. 8-2, p. 255
A T-tubule (or transverse tubule) is a deep invagination of the sarcolemma, which
is the plasma membrane, only found in skeletal and cardiac muscle cells. These
invaginations allow depolarization of the membrane to quickly penetrate to the
interior of the cell.

10. Figure 1.3

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

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

14. Myosin
• Component of thick filament
• Composed of SIX polypeptide chains, two identical
heavy chains, and four light chains.
• The two heavy chains wrap spirally around each other
for form a double helix; however one end of each of
these chains is folded into a globular protein mass called
the head; the elongated portion is called the tail.
• 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

15. Cross Bridges in Myosin Filaments
•The protruding arms and heads together are called
cross-bridges.
•Each cross-bridge is believed to be flexible at two
points called hinges.
•One where the arm leaves the body of the myosin
fiilament.
•Where the two heads attach to the arm.
ATPase activity of Myosin Head
Another feature of myosin head, essential for muscle
contraction is that it functions as an ATPase enzyme.
This property allows the head to cleave ATP and to use
the energy to energize the contraction.

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. The Actin Filament
• The back bone of the actin filament is a double-
stranded F-Actin protein molecule.
• Each strand of double F-actin helix is composed of
polymerized G-actin molecules.
• Attached to each one of the G-actin molecules is
one molecule of ADP. It is believed that these ADP
molecules are the active sites on the actin filaments
with which the cross-bridges of the myosin filaments
interact to cause muscle contraction.

19. Composition of a Thin Filament

20. • A pure actin filament without the presence of
troponin-tropomyosin complex binds strongly with
myosin molecules, in the presence of Magnesium
and ATP.
• However if the troponin-tropomyosin complex is
added to the actin filament, this binding does not
take place.
• Thus the active sites on the normal actin filament of
relaxed muscle are inhibited or actually physically
covered by the troponin- tropomyosin complex.
• For contraction to take place the inhibitory effect of
the T-T complex must itself be inhibbitted.

21. 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.

22. Large amount of Calcium Ion
• In the presence of large amounts of calcium ions the
inhibitory effect of T-T complex is inhibited.
• Calcium ion combines with troponin-C, the Troponin
complex undergoes conformational change that
moves it deeper into the groove between the two
actin strands.
• This uncovers the active sites of the actin , thus
allowing the contraction to proceed.

23. 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+

24. Role of Calcium in Cross-Bridge Formation

25. Cross-bridge interaction between actin and
myosin brings about muscle contraction by
means of the “Sliding Filament Mechanism.”
Walk-Along Theory of Contraction

26. 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

27. 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

28. Figure 1.5

29. Fig. 8-9, p. 260
Basic 4 steps

30. 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

31. 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

32. 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

33. Changes in Banding Pattern During Shortening

34. 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

35. Rigor Mortis
• Rigidity caused by loss of all the ATP which is
required to cause the separation of the cross-
bridges from the actin filament during the relaxation
process.
• Thus, several hours after death the muscles of the
body go into a state of contracture, called “ Rigor
Mortis”, i.e. the muscle contracts and becomes rigid
even without action potential.
• The muscle remains in rigor until the muscle
proteins are destroyed by autolysis

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

37. T Tubules and Sarcoplasmic Reticulum

38. 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)

39. 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

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

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

42. 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

43. 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

44. Motor Unit Recruitment
• 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

45. 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

46. Schematic Representation of Motor Units in
Skeletal Muscle

47. Twitch Summation and Tetanus
• Twitch summation
– 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

48. Summation and Tetanus

49. 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

50. Fig. 8-17, p. 268

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

52. 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

53. 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

54. 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

55. 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

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

57. 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

58. Characteristics of
Skeletal Muscle
Fibers

59. 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

60. 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

61. Muscle Spindle Function

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

63. 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

64. Patellar Tendon Reflex

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

66. 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

67. 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

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

69. Calcium Activation of Myosin Cross Bridge in Smooth Muscle

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

71. Smooth Muscle
• Two major types
– Multiunit smooth muscle
– Single-unit smooth muscle

72. 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

73. 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

74. 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