DR IRAM IQBALApr 8, 2023 1

Sequence Overview and classification of muscles.Skeletal muscles

Myofibrils and myofilamentsThe contraction cycleMotor innervationSensory innervationDevelopment ,healing & repair

Cardiac muscleStructure of cardiac muscleInjury and repair

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Smooth musclesStructure of smooth muscleFunctional aspects of smooth muscleRenewal repair and differentiation

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DEFINITIONAggregates of specialized ,elongated cells arranged in parallel array , whose primary role is contraction.

Muscle tissue is responsible for movement of body and its

parts and for change in size and shape of internal organs.

Muscle cells are known as fibers as there is elongation of

cells in axis of contraction

All are derived embryonically from mesenchyme Apr 8, 2023 4

Muscle TissuesMuscle tissue is contractile, meaning it can

shorten itself. Three characteristics help us tell the types

apart: The cell shape, The placement and number of nuclei, The level of oraganization of the contractile

fibers, actin and myosin (ie. whether its striated or nostriated ).

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CLASSIFICATION OF MUSCLESOn the basis of appearance of contractile cells

STRIATED MUSCLES Skeletal musclesVisceral striated muscles Cardiac muscles

NON-STRIATED MUSCLES Smooth muscles Functional classification

1. Voluntary2. Involuntary.

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Types of muscle

Skeletal muscle: which is striated and voluntary

Cardiac muscle: which is striated and involuntary

Smooth muscle: which is non striated and involuntary

 

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Skeletal muscles Smooth musclesCardiac muscles

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MUSCLE TERMINOLOGY

Myofiber or myocyte: a muscle cell:Sarcolemma the plasma membrane of a

muscle cell,its external lamina & its surrounding reticular fibers.

Sarcoplasm: the cytoplasm of the muscle cellSarcoplasmic reticulum: the endoplasmic

reticulum of a muscle cellSarcosome: the mitochondria of a muscle cellSarcomere: the contractile or functional unit

of muscle

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SKELETAL MUSCLESA multinucleated syncitiumConsists of striated muscle fibers held together by C.T.ColorShape, polygonal

Length UP TO 100CM

Diameter 10-100um

Basal laminaSarcolemma NucleiSarcoplasm

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SKELETAL MUSCLECells of this tissue are polygonal and run the length of the muscle.

The cells are so long, their many nuclei are spread the length of the cell.

The actin and myosin are very highly organized so striations are prominant. The strands of actin and myosin are compacted into the center of the cell which causes the nuclei to be pushed to the periphery of the cell, just inside the cell membrane.

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L.S. of skeletal musclesApr 8, 2023 13

LAYERS OF CONNECTIVE TISSUESkeletal muscle cells have

a dense connective tissue layer around their cell membranes called the endomysium.

The cells are grouped together into groups called fascicles

Fascicles are surrounded by another layer of dense connective tissue called the perimysium.

Many fascicles are grouped into a single muscle which is wrapped with a 3rd dense CT layer, the epimysium.

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This regular organization

of the myofibrils gives

rise to the cross-striation,

which characterizes

skeletal and cardiac

muscle. Sets of individual

"stria" within a myofibril

correspond to the

smallest contractile units

of skeletal muscle, the

sarcomeres.15Apr 8, 2023

TYPES OF SKELETAL MUSCLES(according to their speed of contraction & metabolic

activity)

Type 1/ Slow oxidative fibers

Type 11a/ Fast oxidative glycolytic fibers

Type 11b / Fast glycolytic fibers

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Muscle Fiber Characteristics

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MYOFIBRILSStructural & functional subunit of muscle fibers

A myofibril is a cylindrical bundle of contractile proteins found within the muscle cell.

Myofibrils are composed of individual contractile proteins called myofillaments.

These myofilaments are generally divided into thick and thin myofilaments.

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THIN FILAMENTS

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Sarcomere ,portion of myofibral b/w two Z lines

• Measure in relaxed state, 2-3 um• Extreme relaxation & contraction,

1um=4um

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MYOFILAMENTS

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THICK FILAMENTS

a actinin

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The light bands are known as

I bands. The I bands are

composed mainly of actin

filaments. Each I band is

bisected by a protein disc

known as the Z-line.

Actin filaments are anchored

into the Z-line. During muscle

contraction the actin

filaments slide over the

myosin filaments which

results in a shortening of

the I band.Apr 8, 2023

In the middle of the A band is a somewhat lighter area known as the H zone. This zone corresponds to the area where we have myosin not overlapped by actin).

In the middle of the H zone we see a dark band known as the M line.

The M line is comprised of protein fibers that function to anchor the myosin filaments

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THIN FILAMENTThe actin

molecules (or G-actin) are spherical and form long chains. Each thin myofilament contains two such chains that coil around each other.

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Tropomyosin64 kilodalton protein

Consists of double helix of two polypeptides

Form filaments running in grooves b/w F-actin molecules

In resting muscle, tropomyosin & troponin masks myosin binding sites on actin molecule

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TroponinComplex of three globular

subunits

Each tropomyosin molecule

contains one troponin complex

Troponin C

(smallest)

Bind to Ca

Initiation of contraction

Troponin T

Bind to tropomysin

Troponin I

Bind to actin

Inhibiting actin-myosin

interactionApr 8, 2023 29

Myosin 11510 kilodalton protein

Composed of two polypeptide heavy chains& four light chains

Light chains are of two types;

essential light chain,

regulatory light chain.

One molecule of each is present in association with myosin head

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Aggregate in tail to tail to form bipolar thick filaments

Bare zone -------- H band

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MYOSIN HEAD The MYOSIN HEAD has

several important

characteristics:

It has ATP-binding sites into

which fit molecules of ATP. ATP

represents potential energy.

It has ACTIN-binding sites into

which fit molecules of ACTIN..

It has a "hinge"at the point

where it leaves the core of the

thick myofilament. This allows

the head to swivel back and

forth, and the "swivelling"

actually causes muscle

contraction.

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When a muscle contracts, each sarcomere shortens & become thicker, but the myofilaments remain the same length

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Sliding Filament Theory The Force of contraction is generated by the process that

slides the actin filament over the myosin filament

The length of the thick and thin filaments do not change

The length of the sarcomere decreases as actin is pulled

over myosin

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REGULATION OF CONTRACTION

Ca must be available for the reaction b/w actin & myosin. After contraction Ca must be removed . This rapid delivery and removal of Ca is accomplished by the combined work of the Sarcoplasmic reticulum and the transverse tublar system

Calcium

Sarcoplasmic reticulum

Transverse tubular system

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The sarcoplasmic reticulumThe sarcoplasmic

reticulum is the endoplasmic reticulum of the muscle cell. There are sac-like regions of the sarcoplasmic reticulum known as terminal cisternae. The terminal cisternae act as calcium storage sites.

Two terminal cisternae are associated with a T tubule to form a structure known as a triad.

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SARCOPLASMIC RETICULUM

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TRANSVERSE TUBULES (or T-TUBULES for short).

The SARCOLEMMA has a unique feature: it has holes in it. These "holes" lead into tubes called TRANSVERSE TUBULES These tubules pass down into the muscle cell and go around the MYOFIBRILS.

The function of T-TUBULES is to conduct impulses from the surface of the cell (SARCOLEMMA) down into the cell 40Apr 8, 2023

TRANSVERSE TUBULES

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Phases of the Excitation Contraction Coupling (ECC)

1. Resting

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2. voltage sensor

proteinPotent

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Muscle contractionBecause skeletal muscle is voluntary muscle,

contraction requires a nervous impulse. So, step 1 in contraction is when the impulse is transferred from a neuron to the SARCOLEMMA of a muscle cell.

The impulse travels along the SARCOLEMMA and down the T-TUBULES.. From the T-TUBULES, the impulse passes to the SARCOPLASMIC RETICULUM.

As the impulse travels along the Sarcoplasmic Reticulum (SR), the calcium gates in the membrane of the SR open. As a result, CALCIUM diffuses out of the SR and among the myofilaments.

Calcium fills the binding sites in the TROPONIN molecules. this alters the shape and position of the TROPONIN which in turn causes movement of the attached TROPOMYOSIN molecule.

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Movement of TROPOMYOSIN permits the MYOSIN HEAD to contact ACTIN.

Contact with ACTIN causes the MYOSIN HEAD to swivel

During the swivel, the MYOSIN HEAD is firmly attached to ACTIN. So, when the HEAD swivels it pulls the ACTIN

At the end of the swivel, ATP fits into the binding site on the cross-bridge & this breaks the bond between the cross-bridge (myosin) and actin. The MYOSIN HEAD then swivels back. As it swivels back, the ATP breaks down to ADP & P and the cross-bridge again binds to an actin molecule.

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THE CONTRACTION CYCLE

1. Attachment

2. Release

3. Bending

4. Force generation

5. Reattachment

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CARDIAC MUSCLES

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Elongated, branching cells with irregular contours at their junctions

Sarcolemma

Nuclei

Myofibrils

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CARDIAC MUSCLE

Cardiac muscle cells are not as long as skeletal muscles cells

Often are branched cells

Cardiac muscle cells may be mononucleated or binucleated.

Nuclei are located centrally in the cell.

TEM reveals,that myofibrils of the cardiac muscle separate to pass around the nucleus.

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Outlining a biconical juxtanuclear region in which cell organelles are concentrated

Region is rich in mitochondria & contains the golgi apparatus, lipofuscin pigments, and glycogen.

In the atria atrial granules are also concentrated in the juxtanuclear cytoplasm

Contain two polypeptide hormones’Atrial natriuretic factor (ANF)Brain natriuretic factor(BNF)

Both are diuretics, effecting urinary excretion of Na Inhibit Renin by kidney inhibit Aldosterone by adrenal gland

Cardiac muscle is striated. In addition cardiac muscle contains intercalated

discs

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Intercalated discsIntercalated discs

invariably occur at the ends of cardiac muscle cells in a region corresponding to the Z-line of the myofibrilsIt consists of a transverse component and a lateral component.Both components of disc contain specialized cell to cell junctions between adjoining muscle cells.

Fascia adherensMaculae adherenesGap junctions

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L.S. OF CARDIAC MUSCLE

T.S. OF CARDIAC MUSCLEApr 8, 2023 58

Sarcoplasmic Reticulum

Narrow cisternae, coursing longitudinally

Anastomosing forming a plexiform pattern

T tubules

Wider lumen

Course mainly in transverse direction

Seen at the level of Z disc

DIAD

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SARCOPLASMIC RETICULUMT-tubules are typically

wider than in skeletal muscle, but there is only one T-tubule set for each sarcomere,

It is located close to the Z-line.

It does not form continuous cisternae but instead an irregular tubular network around the sarcomere with only small isolated dilations in association with the T-tubules. 60Apr 8, 2023

CONTRACTION CYCLEPassage of calcium from the lumen of T tubule to the sarcoplasm of a cardiac muscle cell is essential to initiate the contraction cycle.In the first stage of the cardiac muscle contraction cycle, Ca2+ from the lumen of the T tubule is transported to the sarcoplasm of cardiac muscle, which opens gated Ca2+ -release channels in adjacent terminal sacs of the sarcoplasmic reticulum. This “calcium triggered calcium release mechanism” causes a massive and rapid release of additional calcium that initiates subsequent steps of the contraction cycle, which are identical to those in skeletal muscle.

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The difference b/w initiation of cardiac and skeletal muscle contraction- the long –lasting membrane depolarization and activation of voltage-sensitive Ca channels in the wall of the T tubule–

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Injury and repairLocalized injury-------death of tissue-----

replaced with fibrous connective tissue------cardiac function is lost at the site of injury------seen in non fatal MI.

Confirmation of suspected MI can be made through the detection of TnI &TnT IN THE BLOOD

Released In Blood Stream Within 3-12 hrsRemain elevated up to two wks.

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SMOOTH MUSCLEGenerally occur in the form of bundles or sheets of elongated fusiform cells with finally tapered ends.

Length 20um small blood vessels200um small intestine500um in wall of uterus

abundant cytoplasmic. Smooth muscle cells have a

single centrally located nucleus often has corkscrew appearance in LS. (contraction of cell during fixation)(differ from fibroblast)

In noncontracted cell, nucleus is elongated with tapering end.

organelles are concentrated at each end of nucleus 65Apr 8, 2023

SMOOTH MUSCLESSmooth muscle cells do

not have visible striations although they do contain the same contractile proteins as skeletal and cardiac muscle, these proteins are just laid out in a different pattern

Interconnected by gap junctions (specialized communication junction)Apr 8, 2023 66

GAP JUNCTIONS

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COMPONENTS OF CONTRACTILE APPARATUS

Thin filaments actin tropomyosin caldesmon calponin

Thick filaments myosin II

(no troponin is associated with Sm tropomysin) 68

Cytoskeleton (intermediate filament)

desmin vimentin

Structure of smooth muscle

Apr 8, 2023

Structure of smooth muscle Smooth muscles cells posses a contractile

apparatus of thin & thick filaments and a

cytoskeleton of desmin and vimentin

intermediate filament

The thin filaments in SM are attached to dense

bodies that are visible among the filament’

Dense bodies are distributed through out the

sarcoplasm in a network of intermediate

filaments containing the protein desmin

(vascular SM contain desmin+vimentin) which

are part of the cytoskeleton of the cell.

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Dense bodies contain a verity of attachment plaque protein including a-actinin which anchors both thin filaments &intermediate filaments either directly or indirectly to the sarcolemma. Transmitting contractile forces generated inside the cell to the cell surface.( Analogue to Z –line)

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Calmodulin is Ca binding protein ,related to TnC found in skeletal muscles ,regulate the intracellular concentration of Ca

Calcium does not bind to troponin but, rather, to a protein called calmodulin. The calcium-calmodulin complex binds to myosin light chain kinase (MLCK) 'activates' myosin which then binds to actin & contraction begins

The calcium-calmodulin complex may also bind with caldesmon regulate its phosphorylation and releases from F-actin

Cells do not have t-tubules & have very little sarcoplasmic reticulum

Cells do not contain sarcomeres (so are not striated).

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CONTRACTION IN SMOOTH MUSCLES

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Structure of thick filaments In smooth muscles is different than in skeletal musclesRather than a bipolar

arrangement ,myosin II molecules are oriented in one direction on one side of the filament band in an opposite direction on the other side of the filament.

No central bare zone but instead has asymmetrically tapered bare end.Apr 8, 2023 74

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Plasma membrane in high resolution TEM is characterized by numerous invaginations of cell membranous that resumble caveolae .

The caveolae and underlying vesicles along with the sER function in a manner analogue to the T -system of the striated muscles to deliver Ca to the cytoplasm

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COMPARISON OF THREE MUSCLE TYPES

STRUCTURAL FEATURES

Muscle cellLocalityC.T. componentsFiberStriationNucleusT tubulesCell to cell junctionSpecial features

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Comparison of three muscle typeskeletal cardiac smooth

Structural features

Long elongated cell diameter(10-100um)Length up to 100cm

Short narrow cell D =10-15umL=80-100um

short elongated ,fusiform.D=2-2um,L=20-200um

Location Muscles of skeletonVisceral striated

Heart, SVC, IVC, pulmonary vein

Vessels, organs,& viscera

Connective tissue components

Epimysium, perimysium, endomysium

Endomysium (sub endocardial & subpericardial,CT)

Endomysium. sheaths &bundles

fibre Single skeletal muscle cell

Linear. branched arrangement of several CM

single smooth muscle cell

striation Present Present None

nucleus Many peripheral Single central, juxtanuclear region

Single central

T-tubules Present at A –I junction, triad; 2 T-tubules/sarcomere

Present at Z lineDiad. one T-tubule/sarcomere

None ,well developed sER many invaginations

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Skeletal Cardiac Smooth

Cell to cell junction

None Intercalated disksFasciae adherentesMacula adherentsGap junctions

Gap junctions (nexus)

Special features Well-developed sER & T-tubules

Intercalated disks Dense bodies, caveolae & Cytomlasmic vesicles

FunctionsType of innervation

Voluntary Involuntary Involuntary

Efferent innervation

Somatic Autonomic Autonomic

Type of contraction

All or none All or none Slow, partial,rhythmic

Regulation of contraction

By binding Ca to TnC causes trypomysin movement &exposes myosin binding site on actin filament

By binding Ca to TnC causes trypomysin movement &exposes myosin binding site on actin filament

By phosphorylation of myosin light chain by myosin light chain kinase in the presence of Ca-calmodin complex

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Skeletal Cardiac Smooth

Growth and generationMitosis

None None (in normal conditions )

Present

Response to demand

Hypertrophy Hypertrophy Hypertrophy & hyperplasia

Regenration Limited ,satellite cells & myogenic cells from bone marrow

None in normal condation

present

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Skeletal muscles Smooth muscles Cardiac muscles

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REFERENCESText and Atlas of Histology by MICHAEL H. ROSS, 5th Edition.

Google search results for images

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BAILEY’S Textbook Of Microscopic Anatomy, 18th Edition

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