Block 2 Respiratory and Renal Physiology

UNIT 12
MUSCULOSKELETAL SYSTEM

Structure
12. 1 Introduction Cardiac Muscle Cells

Expected Learning 12.6 Physiology of Muscle

Outcomes Contraction: Striated and
Non-Striated Muscle
12.2 Biological significance of
Musculoskeletal System Excitation-Contraction
Coupling
12.3 Anatomy of Bone
Contraction of Skeletal
Compact Bone
Muscles
Spongy Bone
Contraction of smooth
Bone Cells Muscles

12.4 Formation of Bones 12.7 Summary

12.5 Structure of Muscles 12.8. Terminal Questions

Skeletal Muscle Cells 12.9 Answers

Smooth Muscle Cells

12.1 INTRODUCTION
This unit deals with the structure and functions of human skeleton and
muscular system. You know that the human body has intricately
interconnected musculoskeletal network. This intricate nature of
musculoskeletal interconnection provides the body with a proper form,
stability, voluntary movement, and robustness. The musculoskeletal
organization is made up of many different structural elements such as bones,
joints, ligaments, tendons and the voluntary muscle tissue of the body that
support the organism with the day-to-day activities. The ‘contraction force’ is
then transferred to the skeletal elements resulting in the movement of body
parts. Our body has specialized contractile cells; the muscle cells; which
240 generate motile forces via contraction, which is the direct manifestation of the
Unit 12 Musculoskeletal System

interaction of the ‘contractile proteins’ actin and myosin. The contractile

proteins, in association with other components of myofilaments and affiliated
proteins, work in unison to generate the motor forces necessary for cellular
contraction.

In this unit, you will study about structure and function of bone and muscle
cells. You will also learn about the structural components of skeletal muscle,
smooth muscle and cardiac muscles. The role of sarcomere, actin, myosin and
troponin and calcium in muscular contraction is also described.

Expected Learning Outcomes

After studying this unit, you should be able to:

 explain gross anatomy of bones;

 identify of bone tissue and cells and their functions;

 explain structure of osteon;

 discuss the osteogenesis and distinguish between intramembranous

ossification and endochondral ossification;

 describe structure of the smooth, skeletal muscle and cardiac cells and
differentiate between them;

 highlight the role of calcium in Excitation–contraction coupling ; and

 enlist the steps of muscle contraction.

12.2 BIOLOGICAL SIGNIFICANCE OF

MUSCULOSKELETAL SYSTEM
Musculoskeletal system consists of muscles, bones, cartilage, ligaments,
joints, and other connective tissues. Its primary function is the movement of
body and it also keeps organs in place and, gives support and protection to
the body. The skeleton system is a complex structure consisting of bones and
cartilage. Human body has a total of 206 bones with two distinct divisions. The
bones vary in shape and are classified as long, short, flat and irregular based
on their shape.

Our body has three types of muscle cells; skeletal muscles, cardiac muscles
and smooth muscles; among which the skeletal muscles and smooth muscles
are part of musculoskeletal system. Skeletal muscles are ‘striated muscles’
associated with the bones and are the only ‘voluntary muscles’. The cardiac
muscles are present only in the heart and are striated and involuntary in
nature. Smooth muscles are present in the lumen of the hollow organs of GIT,
blood vessels, urinary bladder etc. Their primary function is the contraction;
and help in the movement of food material and substances such as bile and
enzymes through the gastrointestinal tract. The smooth muscles adjust blood
vessel's diameter and thus regulate the rate of blood flow.

The musculoskeletal system performs several basic functions:

241
Block 4 Musculoskeletal and Nervous Physiology
 Support: The skeleton serves as the structural framework for the body
by supporting soft tissues and providing attachment points for the
tendons of most skeletal muscles.

 Protection: The skeleton protects the most important internal organs

from injury. For example, cranial bones protect the brain, vertebrae
(backbones) protect the spinal cord, and the rib cage protects the heart
and lungs.

 Assistance in body movement: Most skeletal muscles are attached to

the bones. Their contraction pull bones to produce movement.
Movements of the whole body, such as walking and running, and
localized movements such as grasping a pencil or nodding the head as
a result of muscular contractions, rely on the integrated functioning of
skeletal muscles, bones, and joints.

 Mineral homeostasis: Bone tissue stores several minerals, especially

calcium (about 99%) and phosphorus, which contribute to the strength of
bone. On demand, bone releases minerals into the blood to maintain
critical mineral balances (homeostasis) and to distribute the minerals to
other parts of the body.

 Blood cell production: The developing bones of the fetus and some
adult bones, such as the hip bones, ribs, breastbone, vertebrae
(backbones), skull, and ends of the bones of the arm and thigh have a
connective tissue called red bone marrow. It consists of developing
blood cells, adipocytes, fibroblasts, and macrophages within a network
of reticular fibers; and produces red blood cells, white blood cells, and
platelets by a process, called hemopoiesis.

 Stabilizing body positions: Skeletal muscle contractions stabilize joints

and help maintain body positions, such as standing or sitting. Postural
muscles contract continuously when you are awake; for example,
sustained contractions of your neck muscles hold your head upright.

 Storing and moving substances within the body: Storage is

accomplished by sustained contractions of ring-like bands of smooth
muscle called sphincters, which prevent outflow of the contents of a
hollow organ. Temporary storage of food in the stomach or urine in the
urinary bladder is possible because smooth muscle sphincters close off
the outlets of these organs.

 Generating heat: As muscular tissue contracts, it produces heat, a

process known as thermogenesis. Much of the heat generated by
muscles is used to maintain normal body temperature. Involuntary
contractions of skeletal muscles, known as shivering, can increase the
rate of heat production.

242
Unit 12 Musculoskeletal System

SAQ 1
Fill in the blanks:
i) The skeletal system consists of .......................
ii) The rigid framework of the body is called......................
iii) Calcium is stored mainly in ......................
iv) ................... are the voluntary and striated muscles cells.
v) Cardiac muscles are present only in ............................

12.3 ANATOMY OF BONE

The bone is a crucial living tissue that makes skeletal system of the body. A
bone has two main parts (Fig. 12.3):

1. Diaphysis is hollow and cylindrical main portion of the bone.

2. Epiphyses (-is, sing.) form the bulbous proximal and distal ends of the
bone.

In addition, there are metaphyses - special regions present amid the

diaphysis and the epiphyses which contain the epiphyseal growth plates in
growing bones.

Fig. 12.1: Parts of a long bone. (Image source: http://cnx.org/contents/14fb4ad7-

[email protected]@7.1).OpenStax College.

243
Block 4 Musculoskeletal and Nervous Physiology

The epiphyseal growth plates are layers of specialized hyaline cartilage which
allows the bone to grow in length till 18–21 years of age. Once the bones
cease to grow, the hyaline cartilage of the epiphyseal plate gets replaced by
osseous material resulting in the formation of a bony structure called the
‘epiphyseal line’. The articular facets/tips of epiphyses are covered and
protected by is a thin layer of hyaline cartilage called ‘articular cartilage’ (Fig.
12.3). It forms the ‘articulation’ (joint) with another bone, reduces friction and
absorbs shock.

The long cylindrical shaft of diaphysis encloses a ‘medullary cavity’ or

‘marrow cavity’, which is filled with the red bone marrow or fatty yellow
bone marrow in adults. The walls of the diaphysis are composed of dense
and hard compact bone.

Almost the entire external surface of the bone is covered by a tough dense
fibrous sheath called ‘periosteum’ except the articular cartilage. The muscles,
tendons, and ligaments are inserted into the periosteum. The internal surface
of the medullary cavity of bone is lined by a thin cellular membrane,
endosteum. The inner surface of the bone (in the marrow cavity) is spongy.
Bones also have subchondral smooth tissue present at their ends which is
covered with cartilage (Fig. 12.2).

Thus, based on the presence of compact and spongy tissues, bones are
categorized into compact and spongy bones.

Fig. 12.2: Anatomical structure of bone.

12.3.1 Compact Bone

In the wall of the long bones, the bony material is compressed and compacted
making it a very hard structure, hence such bones are also known as

244
Unit 12 Musculoskeletal System

‘compact bones’. The hard wall of compact bones is made of numerous

hollow, long, multi-layered bony columns referred to as ‘osteons’.

The osteon is made of ‘osseous tissue’- a tough organic material (mostly

collagen fibers and some homogeneous gelatinous substance- the ground
substance), which later gets mineralized and hardened. The osteons run
parallel to the long axis of the bone, in the line of stress exerted on them. Each
multilayered osteon column is made up of concentric layers of lamellae
arranged around a ‘central channel’ called ‘Haversian canal’ (or ‘canals of
Havers’). The central canal contains blood vessels, lymphatics and nerves
(neurovascular bundles). These neurovascular channels of Havers along with
their concentric bony lamellae form the ‘Haversian system’ or ‘osteon’. The
canals, with their neurovascular bundles, remain connected with one another,
and with the endosteum and periosteum via ‘Volkmann's canals’ or
‘perforating canals’ which pierce the columns horizontally (at right angles to
the long axis of the bone) or obliquely to the Haversian canals (Fig. 12.3a&b).

Fig. 12.3(a) Structure of an osteon showing both compact and spongy bone. The
arrangement of osteocytes forming the lamellae around a single Haversian
canal (b) Transverse section of a compact bone's cortex. (a-Image
attribution:http://cnx.org/contents/[email protected]:rZudN6XP@2/Introduction)
(b) https://commons.wikimedia.org/wiki/File:Transverse_section_of_bone_en.sg
under licensed: Creative Commons Attribution-Share Alike 4.0 International

12.3.2 Spongy Bone

The spongy bone tissue is always located in the medullary cavities or diploë of
a bone, protected by a covering of compact bone. It is strategically located
where bones are not heavily stressed or where stresses are applied from
many different directions. The spongy bone tissue makes the bulk of the
epiphyses of long bones, where it is present beneath a paper-thin protective
layer of compact bone; whereas, it lines the medullary cavities of long bones
245
Block 4 Musculoskeletal and Nervous Physiology

and makes the interiors of most of the short, flat, sesamoid, and irregularly-
shaped bones.

Unlike the hard, compact bone tissue, the spongy bone, known as
‘trabecular’ or ‘cancellous’ bone, does not contain discrete osteons (Fig.
12.4). It consists of an irregular pattern of thin columns called trabeculae. The
individual trabeculae are made of ‘concentric lamellae’, wherein the
osteocytes lie in lacunae and extend their cytoplasmic processes through the
fine minute canaliculi that radiate outward from the lacunae. The wide
gaps/interstitial spaces between the trabeculae are filled with the red bone
marrow in hematopoietically active bones, and with yellow bone marrow
(adipose tissue) in others. Both contain numerous small blood vessels that
supply nutrients to the osteocytes.

Fig. 12.4: Structure of spongy bone.

12.3.3 Bone Cells

The bone tissue contains four types of cells: (a) osteogenic cells, (b)
osteoblasts, (c) osteocytes, and (d) osteoclasts.

(a) Osteogenic cells or Osteoprogenitor cells are the uncommitted,

unspecialized stem cells of bone which give rise to the bone-forming
osteoblasts. They are derived from mesenchymal tissue and are the only
cells that undergo mitotic cell division in a bone. These stem cells are
found in the lining along the inner portion of the periosteum, in the
endosteum, and in the central canals of osteons (Fig.12.5).

(b) Osteoblasts are the bone-forming cells. They secrete, around

themselves, the organic osseous material, mainly containing collagen
fibers, and other organic components needed to build the extracellular
matrix (ECM) of bone tissue. Following the secretion of bone ECM, they
246
Unit 12 Musculoskeletal System

initiate bone hardening process called ‘calcification / mineralization’,

and the individual osteoblasts transform into ‘osteocytes’.

(c) Osteocytes are the mature bone cells and cannot divide. They are the
main cells in bone tissue which maintain and monitor the tissue of its
daily metabolism, such as the exchange of nutrients and wastes with the
blood. The osteocytes are surrounded with and embedded into ECM of
bone; trapped/enclosed singly within lacunae. These cells are involved
in maintaining the bone matrix and their death is followed by resorption
of the matrix.

(d) Osteoclasts are giant, multi-nucleated motile cells of the bone, derived
from the fusion of as many as 50 bone marrow-derived blood
monocytes. They are mostly present concentrated in the endosteum.
One side of the cell that faces the bone surface, has its plasma
membrane deeply folded into a ruffled border from where they release
lysosomal lytic enzymes and acids that digest the protein and mineral
components of the underlying bone matrix. This process of breaking-
down of bone matrix is known as ‘bone resorption’. In these areas, the
osteoclasts lie within enzymatically engraved depressions in the matrix
known as resorption bays (or Howship lacunae). The resorption is
part of the normal development, maintenance, and repair of bone, which
is under the control of hormones such as parathormone, calcitonin etc.
Osteoclasts help in regulating the blood calcium level.

Fig. 12.5: Types of cells in bone tissue.

247
Block 4 Musculoskeletal and Nervous Physiology

SAQ 2
(a) Fill in the blanks:
i) The membrane that covers the bone is known as ...............
ii) Microscopic unit of a bone is .........................
iii) A circular and tubular structure within bone is called............
iv) The irregular pattern of trabeculae form the ...............................
v) A specific region between diaphysis and the epiphyses is called
...............
vi) The cells of bone are..........................
(b) The bone is among the hardest parts of the body. Is bone live or
lifeless?
(c) Enlist the basic parts of the bones.
(d) Name the tissues of bones.

12.4 FORMATION OF BONES

You studied in the earlier section that the basic structural and functional unit of
a bone is the osteon. It is made of ‘osseous tissue’- a tough organic material
(mostly collagen fibers and some homogeneous gelatinous substance- the
ground substance), which later gets mineralized and hardened. Bone
(osseous) tissue is generally dense and hard connective tissue.

Osteogenesis or Ossification is the process of bone formation. During early

embryonic development, the initiation of bone formation can happen in two
different ways:

i) Intramembranous ossification: The osteoblasts differentiate directly

from the undifferentiated embryonic mesenchymal stem cells and
secrete new bone matrix material, osteoid, which gets calcified later.

ii) Endochondral ossification: The matrix of the preexisting ‘hyaline

cartilage templates’ gets eroded and replaced by osteoblasts, which
then produce the osteoid.

Following both these processes, the bone that is formed first is called primary
or woven bone, which is a temporary bone. The temporary bones are soon
replaced by the definitive secondary or lamellar bones.

In addition, bone formation also occurs in various other situations such as

during the -

(a) infancy, early childhood, and adolescence until bones reach the adult
sizes,

(b) remodeling of bones that occur throughout life, wherein the older bones
are replaced with new ones, and

248
Unit 12 Musculoskeletal System

(c) process of repairing bone fractures and breaks.

i) Intramembranous Ossification:

 It is a process of bone formation, by which most flat bones are formed;

e.g., frontal and parietal bones of the skull, some parts of the occipital
and temporal bones, and the lower and upper jaw bones- the mandibles
and the maxillae, respectively (Fig. 12.6).

 In this process, the bone formation is initiated within a “condensation

layer or membrane” of embryonic mesenchymal tissue.

 Within this cellular membrane, the ‘starting point’ for bone formation is
called an ‘ossification center’, where groups of mesenchymal cells
differentiate into osteoblasts.

Fig. 12.6: The basic steps of Intramembranous Ossification. (a) Development

of the ossification center, (b) calcification, (c) fusion of ossification centers
and formation of trabeculae, and (d) development of the periosteum. In the
end, the primary woven bone is replaced by the compact lamellar bone.

 Osteoblasts clusters then synthesize and secrete the new bone matrix,
called the osteoid, at many spots called ‘Ossification Centers’.

 These centers undergo mineralization/ calcification converting the bone

ECM into a hard, bony material.

 During the process of hardening of the matrix, some osteoblasts get

encapsulated and transform into osteocytes.

 All these individual islands of developing bone, form walls that delineate
elongated cavities containing capillaries, bone marrow cells, and
undifferentiated cells.
249
Block 4 Musculoskeletal and Nervous Physiology

 Many such osteoblast clusters arise almost simultaneously at the

ossification center, and their fusion between the walls gives the bone a
spongy appearance.

 Now, the connective tissue that remains among the bone walls is
penetrated by the newly formed blood vessels (angiogenesis) and
additional undifferentiated mesenchymal cells, giving rise to the bone
marrow.

 The ossification centers of a bone grow radially and finally fuse together,
replacing the original connective tissue with a hard mechanically
supporting structure.

ii) Endochondral Ossification:

 This is the other method of the bone formation wherein the ossification
takes place within a preexisting ‘hyaline cartilage template’ whose shape
resembles a miniature version/model of the future bone, to be formed
(Fig. 12.7).

 The cylindrical bones (long as well as short bones) of the body are
formed by this type of ossification.

 The chondroblasts start to secrete cartilage matrix and produce a

hyaline cartilage model.

 Periosteal capillaries start to grow into the disintegrating calcified

cartilage and induce growth of a ‘primary ossification center’, a region
deep in the matrix where bone tissue will replace most of the cartilage.

 Osteoblasts then actively deposit bone matrix over the remnants of

mineralized cartilage, resulting in the formation of ‘spongy bone
trabeculae’. Then the process of ossification spreads from this location
toward both ends of the cartilage model.

 Secondary ossification centers develop in the epiphyses usually around

the time of birth, when the branches of the epiphyseal artery penetrate
the epiphyses.

 However, no medullary cavities are formed in epiphyses, and spongy

bone remains intact in the interior of the epiphyses.

 A thin layer of hyaline cartilage covers the spongy bone of epiphyses.

In the last stage of prenatal bone development,

 The thin layer of hyaline cartilage that covers the spongy bone of
epiphyses forms the ‘articular cartilage’ where two adjacent bones
articulate at joints.

 The articular cartilage persists throughout adult life and doesn’t

contribute to bone growth.

 The two ossification centers do not merge, some hyaline cartilage is left
unossified in between the two, which forms the epiphyseal (growth)
250 plate.
Unit 12 Musculoskeletal System

 The growth plate connects each epiphysis to the diaphysis. This is the
‘area of growth’ in a long bone until the age of 18-21 years.

 Thereafter, the epiphyseal plate disappears ("epiphyseal closure") at

different times with different bones, and for all bones by about age
twenty-one.

 So, as the individual bones mature, the epiphyseal plate gradually

progresses to become an epiphyseal line, where no growth in length can
occur anymore.

Fig. 12.7: Basic steps of endochondral ossification. (Image credit:

http://cnx.org/contents/[email protected]:rZudN6XP@2/Introduction)

Matrix of Mature Bone

Vitamins A, C, D, and
A mature compact bone is composed of inorganic salts (~70%) and organic minerals such as
bone matrix (30%). calcium, phosphorous,
and magnesium are
 The organic matrix is made of 90 - 95% collagen protein fibers (almost essential for normal
exclusively type I fibers) in a homogeneous gelatinous ground growth of bone.
substance, which makes up the rest. Hormones such as
parathyroid hormone,
 The ground substance is made of extracellular fluid, proteoglycans such growth hormone, and
as ‘chondroitin sulfate & hyaluronic acid’, and a group of non- calcitonin helps in
collagen molecules such as osteocalcin, osteonectin, sialoproteins formation of bone.
etc., believed to regulate the process of bone mineralization. We must include
balanced diet rich food
 Osteocalcin is involved in calcium binding and transportation during the in our diet to meet the
calcification process, daily requirement of
vitamins and minerals
 osteonectin acts as a bridge between collagen and the mineral required for the proper
component, growth of the body.

 sialoproteins are rich in sialic acid and are thought to be responsible for
nucleation of hydroxyapatite crystals and deposition of calcium salts.

251
Block 4 Musculoskeletal and Nervous Physiology

SAQ 3
(a) Fill in the blanks:
i) Bone (osseous) tissue can be described as .................................
ii) What is the template for the formation of long bones?.........................
iii) Vertical growth (length) of a person stops once .............................
(b) Differentiate between intramembranous and endochondral ossification

Now let us understand the structure and function of muscle cells.

12.5 STRUCTURE OF MUSCLE CELLS

All body cells have a universal property of ‘contractility’, but only muscle tissue
has undergone the required modification for optimal use of this attribute.
These specialized contractile cells -muscle cells- generate motile forces via
contraction, which is the direct manifestation of the interaction of the
‘contractile proteins’ actin and myosin. These contractile proteins, in
association with other components of myofilaments and affiliated proteins,
work in unison to generate the motor forces necessary for cellular contraction.

These muscular forces generate momentum in different organs, move different

body parts, and the body as a whole. Some of the cytoplasmic organelles of
muscle cell have acquired highly specialized functionality, and thus special
terminology is used for them; sarcolemma for plasma membrane,
sarcoplasm for cytoplasm, and sarcoplasmic reticulum for smooth
endoplasmic reticulum.

Muscles are of three kinds (Fig. 12.8):

Fig. 12.8: Types of Muscles cells.

252
Unit 12 Musculoskeletal System

1. Skeletal muscles: These muscles are connected to the skeletal

elements and help to move the skeleton and different body parts/organs
such as limbs, the eye ball, the tongue etc. They are under one’s own
voluntary control hence referred to as ‘voluntary muscles’. The
arrangement of the contractile protein filaments in the sarcoplasm
(cytoplasm) gives them a peculiar appearance of prominent wavy cross-
striations in under microscope, hence also referred to as ‘striated
muscle’.

2. Smooth muscles: On the other hand, are so named as, unlike skeletal
muscles, there is no wavy, striated appearance when observed under
microscope. The smooth muscles can be seen restricted mainly to
visceral organs, blood vessels etc. hence the name ‘visceral muscle’.
They are ‘involuntary muscles’ as they are not under voluntary control
but under inherent autonomic and hormonal control.

3. Cardiac muscles: Though, like those of skeletal muscle cells, they

appear striated, they are not under voluntary control. However, they
have many structural and functional attributes that are intermediate to
those of skeletal and smooth muscles. The most important feature of
cardiac muscles is the continuous, rhythmic contractility, because of
which the heart beats continuously.

Let us understand structure of body's muscles cells one by one:

12.5.1 Skeletal Muscle Cells

 The skeletal muscles are made of extremely elongated contractile cells,
which are cylindrical and multinucleated; and are with diameter in the
range of 10–100 μm (Fig. 12.9).

 The multinucleated feature tells about their syncytial nature, i.e., the
individual giant muscle cell is formed by the fusion of embryonic
mesenchymal cells called ‘myoblasts’. The cytoplasm of cells fuses but all
the individual nuclei remain intact resulting in their giant size.

 Because of their elongated nature, they are often called ‘muscle fibers’.

 The nuclei are long and oval, and found at the periphery of the cell just
beneath the cell sarcolemma. This feature helps in discriminating skeletal
muscles from cardiac and smooth muscles, where, often a single nucleus
is present located centrally.

 Each muscle is externally surrounded by a connective tissue sheath called

the ‘epimysium’, whereas, the sarcolemma of individual muscle fibers
(myocytes or muscle cells) is overlaid by a delicate areolar connective
tissue layer called the ‘endomysium’.

 A cluster of 100-150 muscle fibers is ensheathed by a collagenous

supporting tissue sheath called ‘perimysium’ and form a muscle
fascicle.

253
Block 4 Musculoskeletal and Nervous Physiology

Fig. 12.9: Structure of skeletal muscle cells.

Microscopic organization of a skeletal muscle fiber:

 The sarcoplasm (cytoplasm) of a muscle fiber is filled with bundles of

long contractile protein fibrils called the myofibrils (Fig. 12.10). The
fibrils run along the entire length of a muscle cell.

 The sarcoplasm has large amounts of glycerol (source of energy for

muscle cells), a protein called myoglobin (stores oxygen for
metabolism), mitochondria, nuclei in the periphery and the highly
specialized smooth endoplasmic reticulum, the sarcoplasmic
reticulum.

 The sarcoplasmic reticulum forms a network around every single

myofibril.

 The terminal sacs of it, called the terminal cisternae, store calcium
ions, which play a very important role in muscle contraction.

 Each myofibril is made of several repeating units, referred to as

‘sarcomere’, the functional units of the muscle.

 The striated appearance is due to the repeating bands of the actin (form
light I bands) and myosin (form dark A bands) proteins present along the
length of myofibrils.

254
Unit 12 Musculoskeletal System

 Each I band has a dense line running vertically through the middle called
a Z disc or Z line. The Z discs mark the border of sarcomeres. Thus,
one sarcomere is the span between two consecutive Z discs and
contains one entire A band and two halves of an I band.

 The thick filaments interspersed between the thin filaments at the center
of the sarcomere span the entire A band. The thick filaments are bound
to proteins of the M line and to the Z disc across the I bands by a
massive protein called ‘titin’, which has spring-like domains.

 Projections from the thick filaments called cross-bridges extend toward

the thin filaments. Cross-bridges play a fundamental role in muscle
contraction.

Fig. 12.10: Structural organization of a muscle fiber.

The sarcomere itself is bundled within the myofibril that runs the entire length
of the muscle fiber and attaches to the sarcolemma at its end. A sarcomere is
a highly organized structure of contractile thick (myosin) and thin filaments
(actin) along with other regulatory proteins, troponin and tropomyosin (Fig.
12.11). When observed under electron microscope (TEM), an oblique section
of myofibrils shows both A and I bands, and arrangement of thin and thick
myofilament in a hexagonal pattern. They are arranged in such a manner
that each myosin filament contacts with six actin filaments. Large
mitochondria in cross-section and SER cisternae are also present between the
myofibrils.

255
Block 4 Musculoskeletal and Nervous Physiology

Fig. 12.11: Structure of a sarcomere.

12.5.2 Smooth Muscle Cells

 Smooth muscles are ‘involuntary’ in nature, and devoid of wavy striations
(that found in skeletal muscles) as they do not have sarcomeres; hence
the name “smooth” muscles.

 Smooth muscles have two distinct muscle types - the ‘visceral (single-
unit) smooth muscle tissues’ and ‘multi-unit smooth muscle
tissues’.

 The former is abundant in skin, small blood vessels/capillaries, GI tract,

bladder, uterus etc.; whereas the latter is found in the walls of large
arteries, bronchioles, arrector pili of hair follicles, iris and the ciliary body
of eye etc.

 These fibers are covered by endomysium, are spindle-shaped, i.e., wide

at the middle and tapering towards the tips, and have a single nucleus.

 Their size, in a relaxed condition, ranges from 30 to 200 μm (thousands

of times shorter than skeletal muscle fibers).

 Sarcomeres are absent in smooth muscle fibers though the cell’s

sarcoplasm do have actin and myosin contractile proteins, which are
organized into ‘thick’ and ‘thin filaments’.

 The thin filaments are anchored firmly to special structures called ‘dense
bodies’, which are invested in the inner membrane of the sarcolemma
and functionally analogous to the ‘Z-discs’ of skeletal muscle fibers (Fig.
256 12.12).
Unit 12 Musculoskeletal System

 Some of these dense bodies can also be found dispersed throughout the
sarcoplasm. All the dense bodies of a single muscle fiber are
interconnected in a reticular fashion with the help of bundles of stretched
‘intermediate filaments’.

Fig. 12.12: Structure of smooth muscle cells.

12.5.3 Cardiac Muscle Cells

The ‘cardiac muscle tissue’ is a one of its kind, found only in the wall of
heart (Fig.12.13).

Fig. 12.13: Structure of cardiac muscles.

 They are 50–100 μm long and 14 μm in diameter.

 The uniqueness of this tissue is its ‘highly coordinated contractions’ in

order to pump blood into the vessels of the circulatory system.

 Another unique feature is, the cardiac muscle cells are extensively
branched.

 The branched cells are connected to one another at their ends by

specialized wavy structures called the ‘intercalated discs’, which
enable the heart to work as a pump.

257
Block 4 Musculoskeletal and Nervous Physiology

 These discs are formed by the sarcolemma and contain two very
important structures: ‘gap junctions’ and ‘desmosomes’.

 The gap junctions between adjacent cardiac muscle fibers form a sort of
‘electric couplings’ thus creating a ‘functional syncytium’.

 This arrangement of electrically connected cardiac muscle cells allows

quick transmission of action potentials between adjacent fibers, thereby
leading to coordinated contraction of the entire heart.

SAQ 4
(a) Fill in the blanks:

i) ...................................... form most of the heart wall.

ii) ..................is the outermost layer which encloses the entire muscle
iii) The plasma membrane of muscle fiber is known as
.............................
iv) The thread like structures of muscles cells called ................ known
as myofibrils.
v) The functional unit of myofibril is .......................
vi) The highly specialized smooth endoplasmic reticulum in skeletal
muscle cells is called ...........................
vii) ........................... is the source of energy for muscle cells.
viii) Why the muscle cells are that long and multinucleated?
........................... .
ix) What are the long multinuclear cells of muscular tissue called: …
...........................
x) Myofibrils of muscle fibers are made of: ...........................
xi) The branched cardiac muscle cells are connected to one another
by: … ….
xii) The physical contact point between the muscle and nerve:
...........................… .
xiii) The process of interlinking the nerve impulse and muscle
contraction.....

(b) Match the column I with that column II.

Column I Column II

A. Z disc 1. has all thin filaments

B. A-band 2. consists of thick filaments but no
thin filaments
C. I-band 3. Entire length of thick filaments
D. H-line 4. present in the center of H-zone
E. M-line 5. Separates two sarcomere

258
Unit 12 Musculoskeletal System

12.6 PHYSIOLOGY OF MUSCLE

CONTRACTION
All eukaryotic cells have membrane potential or electrical gradient across the
membrane based on movement of positive and negative electrolytes. The
movement of electrical potential is selectively controlled by membrane ion
channels which forms the basis of muscle contraction and relaxation. A
muscle contracts when its fibers receive an input through a somatic motor
neuron.

 The motor neurons innervate the skeletal muscle fibers where the axon
terminal of each motor axon divides into a cluster (> 2000) of synaptic
end bulbs/boutons, each of which forms a junction/synapse with a
muscle fiber called Neuromuscular Junction (NMJ).

 Each synaptic end bulb contains hundreds of membrane-enclosed

‘synaptic vesicles’, each of which contains neurotransmitter
‘acetylcholine’ (Ach) molecules.

 Thus, NMJ is the physical site where the information in the form of an
electrical current (action potential/excitation) gets transformed into
mechanical action which, in turn, gets translates into muscle contraction.

 All the biochemical-mechanical sequence of events leading to

contraction of muscle are collectively called ‘excitation-contraction
coupling’.

12.6.1 Excitation-Contraction (EC) Coupling

Excitation–contraction coupling is the physiological process that converts an
electrical stimulus into a mechanical response. It is the link of action potential
between nerve action and muscle contraction.

The process of EC coupling involves four steps (Fig. 12.14):

 propagation of the action potential into the transverse (T) tubules and
release of Ca2+ from the terminal cisternae (TC) of sarcoplasmic
reticulum,

 activation of the muscle proteins by Ca2+,

 generation of tension by the muscle proteins, and

 relaxation of the muscle.

(a) Release of Ca2+: The action potential reaches NMJ through the motor
neuron, polarizes the motor end plate (MEP), resulting in generation of
graded potential called End Plate Potential (EPP).
 The EPP, in turn, causes an action potential in the post-synaptic
sarcolemma due to the release of Na+, which depolarizes it.
 The depolarization (action potential) spreads across and deeper
into the muscle fiber via the T tubules.

259
Block 4 Musculoskeletal and Nervous Physiology
 Depolarization of the T tubule by the action potential causes the
opening of voltage-gated Ca2+ channels.
 Ca2+ flows out of the TC and into the cytoplasm, thereby raising
the relaxed-state concentration of Ca2+ from 0.1 micromole per litre
to several hundreds of times higher.

Fig. 12.14: Excitation-contraction coupling in a skeletal muscle contraction.

(Image source: https://cnx.org/contents/[email protected]:fEI3C8Ot@10/Preface &
https://commons.wikimedia.org/)

(b) Activation of muscle proteins: For a muscle to contract, the thick and
thin filaments must interact.
 When the cell is at rest, this interaction is inhibited by troponin I
(TnI) of thin filament.
 Ca2+ removes this inhibition by binding to troponin C (TnC) on the
thin filament.

260
Unit 12 Musculoskeletal System
 In the myosin molecule, rotation can occur at two points. First site
is located in the tail region to rotate the molecule outward when the
spacing between the thick and thin filaments changes. The other
site is located at the junction of the head and tail where the cross-
bridge bends generating tension.
 The cross-bridge has myosin-ATPase enzyme which hydrolyzes
ATP and provides the energy for muscle contraction.
(c) Generation of tension: Tension is generated by the cycling of the
cross-bridges, which occurs after they bind to the thin filament.
(d) Relaxation occurs when the Ca2+ ions are removed from the cytoplasm
by Ca2+ active transport pumps (Ca2+-ATPase) located on the
membrane of sarcoplasmic reticulum.

12.6.2 Contraction of Skeletal Muscles

During the contraction of striated muscles (skeletal & cardiac muscles), neither
the thick nor thin filaments change their original length. Rather, the thick and
thin filaments overlap each other and slide past one another. The myosin
heads attach and walk along the thin filaments, a mechanism known as
‘Sliding filament Mechanism’. Contraction is induced when an action
potential arrives at the neuromuscular junction (NMJ), and is transmitted along
the T tubules to the sarcoplasmic reticulum to trigger Ca2+ release. In a
resting muscle, the myosin heads cannot bind to the actin filaments because
the myosin binding sites are concealed by the troponin-tropomyosin complex
on the actin filaments. Calcium ions released, upon neural stimulation, bind to
troponin, changing its shape and moving tropomyosin on the F-actin to reveal
the myosin-binding active sites. Following this, a repeating sequence of
biochemico-mechanical events sets off, leading to a cycle of muscle
contraction (Fig. 12.15). The sequence of events is as follows―
a) ATP hydrolysis and formation of cross bridges: The myosin heads,
which contain an ATP binding site and ATPase activity, hydrolyze ATP
(ATP  ADP + Pi). The energy thus released energizes the myosin
heads, which then interact with their binding sites on the actin filament,
forming characteristic biomechanical structures called the ‘cross
bridges’.
b) Cross bridge cycling and power stroke: Binding of myosin heads to
actin produce a conformational change and pivot (swivel) the myosin
thus generating force, which pulls the thin filaments farther into the A
band, toward the Z disc.
c) The ‘power stroke’ which leads to gradual shortening of sarcomeres.
The cross bridges cycle continuously, generate force and shorten the
sarcomere. A single muscle contraction results from hundreds of these
cycles.
d) Detachment of myosin heads from actin: When the neural impulse
stops (acetylcholine at the NMJ is broken down by
acetylcholinesterase, this stops the stream of action potentials along
the muscle fiber) and levels of free calcium diminish, the myosin heads
detach from their binding sites. Tropomyosin again covers the myosin-
binding sites on actin and the filaments passively slide back and
sarcomeres return to their relaxed length.

261
Block 4 Musculoskeletal and Nervous Physiology
2+
 In the continued presence of Ca and ATP, these attach-pivot-detach
events occur in a repeating cycle, each lasting about 50 milliseconds,
which shortens the sarcomere and contracts the entire muscle.
However, in the absence of ATP, the actin-myosin cross-bridges
become stable, which accounts for the rigidity of skeletal muscles (rigor
mortis) that occurs as mitochondrial activity stops after death.

Fig. 12.15: Sequence of events of Excitation-Contraction (EC) Coupling in

skeletal muscle.

(Image attribution: https://cnx.org/contents/[email protected]:fEI3C8Ot@10/Preface by

OpenStax)

12.6.3 Contraction of Smooth Muscles

The mechanism that controls smooth muscle contraction is different from that
of striated muscles.

262
Unit 12 Musculoskeletal System

 The reason being, though the smooth muscle contains actin and myosin
filaments, it doesn’t possess the normal troponin-tropomyosin complex
that is required for the control of contraction, instead, regulated by
calcium binding protein calmodulin (Fig. 12.16).

Fig. 12.16: Sequence of events of Excitation-Contraction (EC) Coupling

in a smooth muscle.

 Because of their much smaller diameter than skeletal muscle cells, even
the T-tubules are not required to spread the action potential to the deep
interiors of the cell.

 Moreover, the contractile thick and thin filaments of the smooth muscles
are not organized into sarcomeres like that seen in striated muscles.

 Instead, as explained earlier, bundles of large number of actin thin

filaments bind to dense bodies, and the myosin thick filaments can be
seen interspersed among the actin filaments.

 Because of the limited calcium storing capacity of sarcoplasmic

reticulum, the calcium ions required for contraction are pulled in from two
sources- (i) external Ca2+ ions brought in through the ‘slow’ calcium
channels of sarcolemma indentations called ‘calveoli’, and (ii) additional
Ca2+ ions supplied by the sarcoplasmic reticulum of the muscle fibers.

 These Ca2+ ions bind to calcium binding protein calmodulin, forming

‘Ca2+-calmodulin complexes’. 263
Block 4 Musculoskeletal and Nervous Physiology

 The complexes then activate an enzyme called ‘myosin light chain

kinase’, which, in turn, activates the myosin heads by hydrolyzing ATP
to ADP and Pi, with the Pi remain attached to the myosin heads.

 The energized (phosphorylated) myosin heads attach to the binding

sites on the actin filament and pull them towards the center.

 In this manner, the force thus developed pull on the bundles of thin
filaments, and in turn, the dense bodies close together, with some
additional help from the cord-like intermediate filament network attached
to them.

 This arrangement causes the entire muscle fiber to contract in a manner

whereby the pointed ends are pulled toward the center, causing the
midsection to bulge and overall shortening of the muscle.

 In this manner, the muscle continues to contract until the Ca2+ ions are
transported back into the SR and out of the cell by active transport with
the help of ‘ATP-dependent calcium pumps’.

 However, a minimal concentration of calcium (basal levels) remains in

the sarcoplasm, maintains the muscle tone, and keeps the muscle
slightly contracted, which is important especially around blood vessels to
maintain blood flow at a particular pressure.

 As the smooth muscles of viscera and other organs have to function for
long periods without rest, their power output is relatively low, but
constant. Thus, the smooth muscle contractions can continue without
using large amounts of energy.

 They can remain in a state of contraction even after Ca2+ is removed and
myosin kinase is dephosphorylated by the formation of latch-bridges,
which are a type subset of cross-bridges formed between myosin heads
and actin.

 The latch-bridges keep the thick and thin filaments linked together for a
prolonged period, without a need to hydrolyze ATP.

SAQ 5
(a) Fill in the blanks:
i) Calcium, binds with... ...................during skeletal muscle
contraction
ii) The binding sites for the cross‐bridges are located on ...............
iii) The ion ....... is necessary in the chemical events for muscular
contraction.
iv) Thick and thin filament interaction leads to ....................
v) .................................. is the contractile protein of muscles cells.
vi) Calcium associates with ............. during smooth muscle
contraction
(b) Enlist the four steps of EC coupling.

264
Unit 12 Musculoskeletal System

12.7 SUMMARY
 Musculoskeletal system is made up of bones (the skeleton), muscles,
cartilage, ligaments, joints, and other connective tissue. It gives shape
and support and; helps in the movement of the body.

 Bone is the main elements of the human skeleton system. Our body has
206 bones which can be long, flat, short, sesamoid and irregular based
on their shape.

 A long bone is longer bone of the body. It has two parts:

the diaphysis and the epiphysis. The diaphysis is the hollow, tubular
shaft that is present between the proximal and distal ends of the bone.
Inside the long bone is the medullary cavity, an inner cavity filled with
yellow bone marrow in an adult. The outer wall of the diaphysis is hard
that made up of osseous tissue (connective tissues).

 Bone tissue consists of four types of cells; osteoblasts, osteocytes,

osteogenic cells, and osteoclasts. These cells form less than 2% of the
bone mass. Osteogenic cells develop into osteoblasts, the
mononucleate cells from which bones develop. Osteoclasts are
responsible for bone resorption and osteocytes are star-shaped bone
cells found in the cells of mature bone and maintain mineral
concentration of matrix.

 Most bones have varying amount of compact and spongy osseous tissue
based on their overall function. Compact bone is more dense and hard
so that they can hold the compressive forces while spongy bone is a
cancellous and soft bone with lightweight that can readily accommodate
as per changing needs of the body.

 Osteon (or Haversian system) is the structural unit of bone. It is roughly

cylindrical structure that is arranged into a lamellar bone. It is about 0.2
mm in diameter. Each ring of osteon is composed of collagen fiber and
calcified matrix called lamella. The collagen fibers and lamella run
parallel twisting each other in multiple directions. The lamellae run at
perpendicular angles to each other, allowing osteons to resist twisting
forces. Inside the osteon, a central canal, or Haversian canal contains
blood vessels, nerves, and lymphatic vessels that supply the nutrient
and electrolytes-rich blood.

 Osteogenesis is the process of development of bone. It is of two types:

intramembranous ossification process form bone from fibrous
membranes while endochondral ossification develops bone from the
hyaline cartilage.

 The structure and function of bones are supported and coordinated by

muscle cells. There are three types of body's muscle cells: Skeletal
muscle, cardiac muscle and smooth muscle. Skeletal muscles are
associated with skeletal structures (bone), cardiac muscle are restricted
to heart and smooth muscle form the lumen of GIT, blood vessels etc.

265
Block 4 Musculoskeletal and Nervous Physiology

 Muscle cells have a universal property of ‘contractility’ which can do

modification for optimal use of this attribute. The muscle cells are often
known as called ‘muscle fibers’.

 Skeletal muscles are generally extremely elongated, cylindrical and

multinucleated contractile cells. They are closely associated with bones
and help to move the skeleton and different body parts/organs. They are
voluntary and striated muscles. The sarcoplasm (cytoplasm) of a muscle
fiber is bound with long bundles of contractile protein fibrils called the
‘myofibrils’.

 Sarcomere is the functional units of the muscle. The thick filaments and
thin filaments are connected with the sarcomere and are inter-dispersed
and coordinated with the A band, M line and Z disc across the I bands
by a massive protein called ‘titin’. The dark areas in the center of the
sarcomere are called A bands. The light areas on either side of the Z
disc are called I bands which contain only thin filaments. Each I band is
bisected by a Z line. Thus, each sarcomere has 2 half I bands, one each
on either end of it.

 Smooth muscles are ‘involuntary’ in nature, and devoid of wavy striations

as they do not have sarcomeres; hence the name “smooth” muscles.
They form two distinct muscle types; the ‘visceral (single-unit) smooth
muscle tissues’ and ‘multiunit smooth muscle tissues’. Smooth muscles
rich in contractile proteins, actin and myosin, are organized into ‘thick’
and ‘thin filaments’. They have dense bodies that are interconnected in a
reticular fashion with the help of bundles of stretched ‘intermediate
filaments’.

 Cardiac muscles are striated like skeletal muscle cells and present in
only in heart. They constantly perform rhythmic contractility, because of
which the heart beats continuously.

 Excitation–contraction coupling is process of skeletal muscle contraction

in which an electrical potential converts to a mechanical response. The
sarcoplasmic reticulum is a specialized endoplasmic reticulum that
release calcium ion which causes muscle to contract. This process is
mediated by the neurotransmitter Acetylcholine (ACh) that binds to
receptors in the motor end plate.

 During the contraction of striated muscles, the length of thick or thin

filaments does not change. Instead, these filaments overlap and slide
past one another. The myosin heads attach and walk along the thin
filaments, a mechanism known as ‘Sliding filament Mechanism’.

12.8 TERMINAL QUESTIONS

1. Discuss in detail the gross anatomy of a long bone.

2. Discuss the structural organization of spongy bone.

3. Explain the process of bone formation.
4. Discuss the histology of bone.
266
Unit 12 Musculoskeletal System
5. Give an account of the structure and function of skeletal, cardiac and
smooth muscle.
6. Draw the labeled diagram of sarcomere.
7. Describe and contrast the process of contraction of skeletal muscles and
smooth muscles.

8. Explain what is excitation contraction coupling.

9. Differentiate between skeletal muscles and smooth muscles.

12.9 ANSWERS
Self assessment Questions
1. i) bones and cartilage

ii) Skeletal system

iii) Axial and appendicular

iv) teeth and bone

v) Skeletal muscles

vi) heart.

2. a) i) compact bone

ii) Spongy bone

iii) osteon

iv) Haversian canals.

v) Spongy bone

vi) metaphyses –

vii) osteogenic cells, osteoblasts, osteocytes, and osteoclasts

b) Epiphysis, metaphysis and diaphysis.

c) The bone is very much live. It contains blood vessels and nervous
supply as well.

d) Compact and spongy tissues.

4. a) i) dense, hard connective tissue

ii) Hyaline cartilage templates.

iii) the epiphysis fuses with the diaphysis and epiphyseal

closure occurs.

267
Block 4 Musculoskeletal and Nervous Physiology
b) Intramembranous ossification Indochondral
ossification

It forms flat bone of the skull, Forms most skeletal

temporal bones, jaw bones (long bones) of the
body.

Chondroblasts form the osteoid Chondroblasts

produce a hyaline
cartilage.

A bone is directly formed from a A cartilage is first

mesenchymal connective tissue formed and then is
replaced with bone
for form skeletal.

Intermediate cartilage does not Intermediate

form cartilage is formed

5. a) i) Cardiac muscle cells

ii) Epimysium

iii) Plasmalemma

iv) Myofibrils.

v) Sarcomere

v) Sarcoplasmic reticulum

vi) The glycerol

vii) They are syncytial cells, formed by the fusion of

embryonic myoblasts.

viii) muscle fibers.

ix) Contractile proteins organized into sarcomeres.

x) intercalated discs.

xi) neuromuscular junction.

xii) Excitation-contraction (EC) coupling.

b) A-5, B-3, C-1, D-2, E 4

6. i) Troponin
ii) Actin.
iii) Calcium
iv) Muscle contraction
v) Myosin.
268
Unit 12 Musculoskeletal System
vi) Calmodulin

Terminal Questions
1. Refer to Section: 12.3. Anatomy of Bone

2. Refer to section 12.3.2. Spongy bone

3. Refer to Section: 12.4. Formation of Bones

4. Refer to Section: 12.3.3 Bone Cells

5. Refer to Sections: 12.5. Structure of Muscle Cells, 12.5.1. Skeletal

muscle cells, 12.5.2. Smooth muscle cells, and 12.5.3. Cardiac muscle
cells

6. Refer to Section: 12.5.1. Skeletal muscle cells and Fig. 12.13 Structure
of a sarcomere.

7. Refer to Sections: 12.6. Physiology of Muscle Contraction. 12.6.1

Excitation-contraction (EC) coupling, 12.6.2 Contraction of skeletal
muscles and 12.6.3. Contraction of smooth muscles

8. Refer to Section: 12.6.1 Excitation-contraction (EC) coupling

9. Refer to Sections: 12.5.1. Skeletal muscle cells and 12.5.2. Smooth

muscle cells.

269