THE MUSCLE TISSUE

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                                          THE MUSCLE TISSUE
                                                Ahmad Aulia Jusuf, MD, PhD
                                                      Depart of Histology
                                          Faculty of Medicine University of Indonesia


                                                               involuntary cardiac muscle limited almost
INTRODUCTION
                                                               exclusively to the heart. The skeletal muscle
   Muscle (Fig-1) is one of the four basic
                                                               (Fig-3) is associated with the bony skeleton
tissue     characterized   by       its      specific
                                                               and consists of cylindrical fibers that are
properties, the ability to convert chemical
                                                               multinucleated.
energy      into     mechanical      work         and
contractility that permit the locomotion,
                                                                     Image removed due to copyright
constriction, pumping and other propulsive
                                                                                  restriction
movement of the muscle to be occured.

                                                                            Fig-3 Skeletal Muscle
     Image removed due to copyright
                                                               The cardiac muscle (Fig-4) consists of
                   restriction
                                                               separate cellular units and is uninucleate.
               Fig-1 The muscle
                                                               Furthermore cardiac muscle is characterized
   There are two major type of muscle
                                                               by     rhythmic,     involuntary   contractions
according to the present of repeating dark
                                                               controlled by autonomic innervation.
and light cross-bands or striation (Fig-2); the

                                                                     Image removed due to copyright
     Image removed due to copyright
                                                                                  restriction
                   restriction

                                                                            Fig-4 Cardiac Muscle
     Image removed due to copyright
                   restriction
                                                                    The smooth muscle (Fig-5) consists of
                                                               spindle-shape, fusiform, uninucleate cell that
   Fig-2 The striated and smooth muscles
                                                               do not exhibit striations. Smooth muscle is

striated muscle and and smooth muscle. The
                                                                     Image removed due to copyright
striated muscle cells display characteristic
                                                                                  restriction
alternation of light and dark cross-bands.
  There are two types of striated muscle;
                                                                            Fig-5 Smooth muscle
skeletal    muscle     accounting         for   most
voluntary muscle mass of the body and
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involuntary and is innervated by the                SKLETAL MUSCLE
autonomic nervous system. Smooth muscle                An anatomically named muscle such as
is    widely   distributed   throughout      the    deltoid muscle consists of many muscle
digestive tube, in the tubular portions of          bundle   or   fascicles    (Fig-8)   which   is
many organs and in the walls of many blood          surrounded by the connective tissue called
vessels.                                            as epimysium. Each muscle bundle consists
     Unique terms are often used in describing
the component of muscle cells (Fig-6).                   Image removed due to copyright
Muscle membran is referred to as sarcolema,                          restriction
the cytoplasm as sarcoplasm, the smooth
endoplasmic     reticulum    as    sarcoplasmic        Fig-8 Organization of skeletal muscle
reticulum and occasionally the mitochondria         of a variable number of muscle fibers
as sarcosomes. The muscle cells frequently          surrounded or delineated by the connective
                                                    tissue, the part of epimysium that extended
      Image removed due to copyright                inward, surrounding the muscle bundles or
                  restriction                       fascicles called as       perimysium. Muscle
                                                    fiber is the basic structural unit of skeletal
      Fig-6 The Organels of muscle fiber            muscle composed by a long, cylindrical and
are called as muscle fiber because they are         multinucleate structure. The muscle fiber is
much longer than they are wide. Unlike the          surrounded by the extension of connective
collagen fibers however they are living             tissue, the perimysium inward called as
entities.                                           endomysium.
     All three muscle types are derived from           All of the connective tissue conducts the
mesoderm. Cardiac muscle originates in              blood vessels, lymphatic vessels, and nerve
splanchnopleuric mesoderm most smooth               into the interior of the muscle, bringing them
muscle is derivated from splanchnic and             close to the individual muscle fibers.
somatic     mesoderm, and         most   skeletal      Muscle fiber (Fig-6 and 9) is a long,
muscles originate from somatic mesoderm.            multinucleated and cylindrical structure with
                                                    1-40 mm in long and 10-100 mikrometer in
      Image removed due to copyright                wide. Numerous nuclei, space along the
                  restriction
                                                         Image removed due to copyright
 Fig-7 Skeletal, smooth and cardiac muscle                           restriction
                                                                                                       3


             Fig-9 The muscle fiber                    THE LIGHT MICROSCOPY OF
length of the fiber are displaced to the               SKELETAL MUSCLE FIBER
periphery by the column of myofibril that                 In the light microscopy, the hemato
occupies the bulk of the sarcoplasm. They              xyllin-eosin    stained      striated     muscle
are flattened against the sarcolemma. The              illustrates alternate light and dark transverse
cytoplasmic surface of the sarcolemma in               binding along the fibers. The hematoxyllin
skeletal muscle is coated with the 400 kD              stainned dark bands (Fig-9and 10) are
protein dystrophin which appears to provide            known     as   A     bands       (anisotropic   or
mechanical reinforcement to the membrane,              biferingent/double refractile with polarized
thereby     protecting   it     against     stresses
developed during muscular contraction.                      Image removed due to copyright
   All of the common cell organelles (Fig-6                               restriction
and 9) are represented in the sarcoplasm,
such as Golgi complex, mitochondria ect.                    Image removed due to copyright
The       sarcoplasm     also      contains     the                       restriction
myoglobin, an oxygen binding protein
which is largely responsible for the slightly            Fig-10 The dark (A) and light (I) bands
brown color of muscle. Myoglobin is                    light) with approximately 1.5 um in length,
present in low concentration and it possibly           while the alternate bands that do not
of little functional significance in the               stainned with hematoxyllin-eosin are the I
relatively pale muscles of humans. As                  bands (isotropic or singly         refractile with
required,      oxygen         dissociates     from     polarized light) with approximately 1 um in
myoglobin and becomes available for                    length. The center of each A band is
oxidations.                                            occupied by a pale area, the H band, which
   The interior of muscle fiber (Fig-9)                is bisected by a thin M line. The I bands is
contains a variable number of longitudinally           bisected by a thin dark line, the Z disk (Z
oriented structural units called as myofibril          line) . The region of the myofibril between
with usually range from 1 to 2 mikrometer              two successive Z disks, known as a
in diameter. Myofibril consists of many                sarcomere, is 2.5 um in length and is
myofilament (more than 100) which are                  considered to be the contratile unit of
oriented longitudinally within the myofibril.          skeletal muscle fibers (Fig-10).
There are two types of myofilament; the                   The term sarcomer refers to the unit of
thick and thin.                                        distance between adjacent Z lines and is the
                                                       fundamental unit of contraction.
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    In a relaxed skeletal muscle fiber (Fig. 9-   overlap     between    the   two    groups   of
10), the thick filaments do not extend the        filaments, effectively reducing the width of
entire length of the sarcomere, whereas the       the I and H bands without influencing the
                                                  width of the A band.
     Image removed due to copyright                  The arrangement of the thick and thin
                  restriction                     filaments bears a specific and constant
                                                  relationship. In mammalian skeletal muscle
                                                  each      thick   filament    is    surrounded
thin filaments projecting from the two Z          equidistantly by six thin filaments (Fig. 9-
disks of the sarcomere meet in the midline.       10). Cross-sections through the region of
Therefore, there are regions of each              over-lapping thin and thick filaments display
sarcomere, on either side of each Z disk,         a hexagonal pattern, with a thick filament is
where only thin filaments are present,            surrounded by six thin filaments.
known as I band which can be seen by the
light microscopy. The region of each              ULTRASTRUCTURE               OF     STRIATED
sarcomere that encompasses the entire             MUSCLE FIBER
length of the thick filaments is the A band.         The fine structure of the sarcolemma is
The zone in the middle of the A band, which       similar to that of other cell membranes.
is devoid of thin filament, is the H band. As     However the distinguishing feature of this
noted earlier, the H band is bisected by the      membrane is that it is continued within the
M line, which consists of myomesin, C             skeletal muscle fiber as numerous T tubules
protein, and other proteins that interconnect     (transverse tubules). T-tubules (Fig.8 and
thick filaments to maintain their specific        11) is a long, tubule extending inward from
lattice arrangement.                              the sarcolemma that penetrate deep into the
    During muscle contraction (Fig-9,10) the      interior of the muscle fiber crossing many
various      transverse     bands       behave    myofibrils.
characteristically.    During       contraction      T tubules pass transversely across the
individual thick and thin filaments do not        fiber and lie specifically in the plane of the
shorten, instead, the two Z disk are brought      junction of the A and I bands in mammalian
closer together as the thin filaments slide       skeletal muscle. One sarcomere has two sets
past the thick filaments (sliding filaments       of T tubules; one at each interface of the A
theory). Thus when contraction occurs, the        and I bands. T-tubules extend deep into the
motion of the thin filaments toward the           interior of the fiber and facilitate the
center of the sarcomere creates a greater
                                                                                                         5


conduction of waves of depolarization along            and vimentin (Fig.12) which secure the
the sarcolemma.                                        periphery of the Z disks of neighboring
   Sarcoplasmic reticulum (Fig. 8 and 11) is           myofibrils to each other. These bundles of
a membrane-bounded tubules that form a                 myofibrils are attached to the cytoplasmic
continuous network occupying the narrow                aspect of the sarcolemma by various
spaces between the myofibrils throughout               proteins, including dystrophin, a protein that
the muscle fiber. Although it corresponds to           binds to actin.
the endoplasmic reticulum of other cells, it                 Deep to the sarcolemma, and inter-
is largely devoid of associated ribosome and           spersed between and among myofibrils are
is specialized for a different function. The           numerous     elongated      mitochondria       with
sarcoplasmic reticulum forms a meshwork                many       highly      interdigitating      cristae.
around each myofibril and displays dilated             Moreover,        numerous      mitochondria     are
terminal cisternae at each A-I junction. Thus          located just deep to the sarcoplasm.
two of these cisternae are always in close
apposition to a T-tubule forming a Triad in            STRUCTURAL ORGANIZATION OF
which a T tubule is flanked by two cisternae.          MYOFIBRILS
   This arrangement permits a wave of                        Electron microscopy demonstrates the
depolarization       to       spread,      almost      presence of parallel, interdigitating thick and
instantaneously, from the surface of the               thin rod-like myofilaments.
sarcolemma throughout the cell, reaching
the terminal cisternae, which have voltage-            THICK FILAMENT
         2+
gated Ca release channel.                                    The thick filaments (15 nm in diameter
   The sarcoplasmic reticulum regulates                and 1.5 um long) are composed of myosin.
muscle        contraction      by       controlled     These     filaments     form     parallel    arrays
sequestering (leading to relaxation) and               interdigitating with the thin filaments in a
                                           2+
release (leading to contraction) of Ca          ions   specific fashion.           The myosin thick
within the sarcopalsm. The wave of                     filament is slightly wider in the middle than
depolarization transmitted by T tubules                at either end.
triggers the opening of the calcium release                  Every thick filament consists of 200 to
channels of the terminal custernae, resulting          300     myosin      molecules.    Each      myosin
in release of calcium into the cytosol in the          molecule (150 nm long; 2 to 3 nm in
vicinity of the myofibrils.                            diameter) is composed of two identical
   Myofibrils are held in register with each           heavy chains and two pairs of light chains.
other by the intermediate filament desmin
                                                                                              6


   The heavy chains resemble two golf
clubs, whose rod-like polypeptide chains are     THE THIN FILAMENT
wrapped around each other in an alpa-helix.         The thin filaments (7nm in diameter
The heavy chains can be cleaved by trypsin       and 1.0um long) are composed primarily of
into a rod-like tail, light meromyosin, and a    actin (Fig-13).
globular head, heavy meromyosin. Heavy              Thin filaments originate at the Z disk
meromyosin is cleaved by papain into two         and project toward the center of the two
globular (S1) moieties and a short, helical,     adjacent   sarcomeres,    thus    pointing   in
rod-like segment (S2) (Fig-13). The S1           opposite directions. A single sarcomere will
subfragment binds adenosine triphosphate         have two groups of parallel arrays of thin
(ATP) and functions in the formation of          filaments, each attached to one Z disk. All of
cross-bridges     between   thick   and   thin   these filaments point toward to the middle of
myofilaments. The heavy chains has two           the sarcomere (Fig-13).
hinges at two different regions: one is at the      The major component of each thin
junction of the LMM and HMM, and the             filament is F-actin, a polymer of globular G-
other is at the neck region near the two         actin unit. Although G-actin molecules are
globular heads (Fig-14).                         globular, they all polymerize in the same
   Light chains are of two types,and one of      spatial orientation, imparting to the filament
each is associated with each S1 subfragment      a distinct polarity. The plus end of each
of the myosin molecule. Each heavy chain                                               -actinin,
has two light chains, and a myosin molecule      the minus end extends toward the center of
is composed of two heavy chains and four         the sarcomere. Each G-actin molecule also
light chains.                                    contains an active site where the head region
    The 200-300 myosin molecule in a thick       (S1 subfragment) of myosin binds. Two
filament are bundle together such that one       chains of F-actin are wound around each
half of the molecules have their heads           other in a tight helix (36-nm periodicity) like
pointing toward the opposite end (Fig-14).       two strands of pearls (Fig-13).
This arrangement result in a bare zone in the       There are shallow grooves along the
center of the A band where there are no          length of the F-actin double-stranded helix.
myosin heads. This molecule organization         Pencil-shaped like tropomyosin molecules
explains in part why two sets of thin            about 40 nm long, polymerize to form head-
filaments in a sarcomere are pulled together     to-tail filaments that occupy the shallow
toward each other that is toward the center      grooves in the actin filaments. Bound
of the A band .                                  tropomyosin masks the active sites on the
                                                                                               7


actin molecules by partially overlapping
them (Fig-13).                                    MUSCLE           CONTRACTION               AND
   Approximately 25 to 30 nm from the             RELAXATION
beginning of each tropomyosin molecule is a          Contraction    effectively    reduces    the
single   troponin     molecule    (Fig.13-15),    resting length of the muscle fiber by an
composed of three globular poly peptides,         amount that is equal to the sum of all
TnT, TnC, and TnI. The TnT subunit binds          shortenings that occur in all sarcomeres of
the entire troponin molecule to tropomyosin;      that particular muscle cell. The process of
TnC has a great affinity for calcium; and TnI     contraction, usually triggered by neural
binds to actin, preventing the interaction        impulses, obeys the “all-or-none law”in that
between actin and myosin (Fig-16)                 a single muscle fiber will either contract or
   Binding of calcium by TnC induces a            not contract as a result of stimulation. The
conformational      shift   in   tropomyosin,     strength of contraction of a gross anatomical
exposing the previously blocked active sites      muscle, such as the biceps, is a function of
on the actin filament, so that myosin heads       the number of muscle fibers that undergo
can bind.                                         contraction. The stimulus is transferred at
   The structural organization of myofibrils      the neuromuscular junction. During muscle
is maintained largely by three proteins, titin,   contraction the thin filaments slide past the
  actinin, and nebulin. Thick filaments are       thick filaments, as proposed by Huxleys
positioned precisely within the sarcomere         sliding filament theory.
with the assistance of titin, a large, linear,    The following sequence of the events leads
elastic protein (Fig-13). A titin molecule        to contraction in skeletal muscle:
extends from each half of a thick filament to     1. Impulse,       generated       along     the
the adjacent Z disk, thus anchoring the               sarcolemma, is transmitted into the
filaments between the two Z disks of each             interior of the fiber via the tubules,
sarcomere. Thin filaments are held in                 where it is conveyed to the terminal
register by the rod-shaped protein            ,       cisternae     of       the    sarcoplasmic
a component of the Z disk that can bind thin          reticulum(see Fig-8,11).
filaments in parallel arrays (Fig-13). In         2. Calcium      ions   leave     the   terminal
addition, two molecules of nebulin-a long,            cisternae through voltage-gated calcium-
nonelastic protein-are wrapped around the             release channels, enter the cytosol, and
entire length of each thin filament, further          bind to the TnC subunit of troponin,
anchoring it in the Z disk and ensuring the           altering its conformation (Fig-16)
maintenance of the specific array (Fig-13).
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3. Conformational          change    in troponin       step that led to contraction. Fisrt calcium
    shifts the position of tropomyosin                 pump in the membrane of the sarcoplasmic
    deeper into the groove, unmasking the              reticulum actively drive Ca2+ back into the
    active site(myosin-binding site) on the            terminal cisternae, where the calcium ions
    actin molecule (Fig-16)                            are bound by the protein calsequestrin. The
4. ATP present on the S1 fragment of                   reduced level of Ca2+ in the cytosol cause
    myosin      is     hydrolyzed,      but     both   TnC to loose its bound Ca2+, tropomyosin
    adenosine        diphosphate     (ADP)      and    then reverts to the position in which it masks
    inorganic        phosphate      (P1)      remain   the active site of actin, preventing the
    attached to the S1 fragment, and the               interaction of actin and myosin.
    complex binds to the active site on
    actin(Fig-16).
5. P1 is released, resulting not only in an
    increased bond strength between the
    actin and myosin but also in a
    conformational alteration of the S1
    fragment.
6. ADP is also released, and the thin
    filament is dragged toward the center of
    the sarcomere(“power stroke”).
7. A new ATP molecule binds to the S1
    fragment, which causes the release of
    the bond between actin and myosin.
The attachment and release cycles must be
repeated numerous times for contraction to
be completed. Each attachment and release
requires ATP for the conversion of chemical
energy into motion.
   As     long        as    cytosolic      calcium
concentration remains high enough, actin
filament will remain in the active stateand
contraction cycles will continue. However
once the stimulation impulses cease, muscle
relaxation occurs involving a reverssal of the

				
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