Histology of the Muscle Tissue

By

Safaa El Bialy (MD, PhD)

Objectives

• Describe the structure of skeletal muscle tissue and its connective tissue components.

• Describe the ultrastructure of the skeletal muscle fiber. • Discuss the role of muscle precursor cells in embryonic development and in

the regeneration of adult muscle. • Distinguish structurally and functionally between cardiac, smooth and

skeletal muscle

Basic Properties of Muscle Tissue

• The cytoplasm of muscle cells is called sarcoplasm• The cell membrane is called sarcolemma• The endoplasmic reticulum is called sarcoplasmic reticulum

Basic Properties of Muscle Tissue

• Properties: • Excitability: ability to respond to a stimulus (normal

reaction when we touch a hot plate)• Conductivity: ability to propagate a response from brain

and nerves to muscles and vice versa)• Contractility: ability to shorten• Relaxability: ability to relax (return to original shape after

contraction)• Elasticity: ability to come back to the original size

Muscles

• We have three types of muscles:

1. Skeletal muscles

2. Cardiac muscles

3. Smooth muscles

Embryological origin of muscles • Muscle cells are of mesodermal

origin• Skeletal muscles derive from

mesoderm of somites• Cardiac muscles derive from

visceral splanchnic meseoderm surrounding the heart tube

• Smooth muscles derive from visceral splanchnic mesoderm surrounding the primitive gut

Organization of Skeletal Muscles

Organization of Muscles

• Epimysium: connective tissue CT around the whole muscle

• Perimysium CT around each bundle• Endomysium CT around each fibre• Connective tissue 1. mechanically transmit the forces

generated by contracting muscle cells2. Is the site of penetration of blood

vessels which run parallel to the muscle fibres

• Some muscles taper into tendons

• EM shows the complex insertion of the collagen fibres of the tendon into the cell membrane of muscle fibres

Skeletal Muscle

• bundles of very long multinucleated cells (fibers)

• Multi-nucleation results from the fusion of embryonic mono-nucleated myoblasts.

• The oval nuclei are usually found at the periphery of the cell under the cell membrane

• The nuclei of cardiac and smooth muscles are centrally located

Skeletal Muscle

• The sarcoplasm is filled with long cylindrical filamentous bundles called myofibrils

• Myofibirls run parallel to the long axis of the muscle

• Longitudinal sections show cross striations of alternating light (I bands) and dark bands (A bands).

• The light bands are bisected by a dark transverse band (Z line)

• The sarcomere (basic contractile unit of the muscle) extends from Z line to Z line

↓ ↓I band A band

Skeletal Muscle

• H band is a lighter zone in the middle of A band and corresponds to myosin molecule

• Bisecting the H band is the M line which is formed mainly of creatine kinase which supply the muscle with ATP

• The sarcomere exhibits a characteristic pattern of transverse striations

• This pattern is due to 2 types of filaments:

• Thick filaments that occupy the centre of the sarcomere

• Thin filaments that run between and parallel to the thick ones

Electron microscope of skeletal muscle

Skeletal Musclem (FYI)

• Medical application:• The variation in diameter of muscle

fibres depends on age, sex, state of nutrition, and physical training

• Hypertrophy: increase in the diameter of individual muscle fibres as well as the formation of new myofibrils (rare)

• Hyperplasia (increase in number of cells), it occurs only in smooth muscles such as the uterus, these muscles did not lose the capacity to divide by mitosis

normal

hypertrophied

Skeletal Muscle• Striated muscle filaments contain 4 main

proteins: actin, tropomyosin, troponin and myosin

• Thin filaments are formed of the 1st three, whereas thick filaments contain mainly myosin

• Actin and myosin represent 55% of the total protein

• Actin is formed of long chains twisted around each other

• Each G actin monomer contains a binding site for myosin

• Tropomyosin a long thin molecule

– 2 polypeptide chains

– run over the actin• Troponin is a complex 3 subunits which

strongly attaches to tropomyosin,

Sarcoplasmic reticulum and transverse tubules

• Depolarization is initiated at a specialized myoneural junction on the surface of the muscle cell

• Results in release of Ca from internal sarcoplasmic reticulum

• Transverse T tubules (near AI junctions) allow flow of calcium into the cell with depolarization

• Adjacent to opposite sides of each T tubule are expanded terminal cisternae of the sarcoplasmic reticulum forming the triad, where depolarization is initiated and is transmitted to the sarcoplasmic reticulum membrane

Muscle contraction

• Resting sarcomeres consist of overlapping thin and thick filaments

• During contraction there is increase in the amount of overlap between these filaments

• Muscle contraction depends on the availability of Ca2+

• And muscle relaxation is related to an absence of Ca2+

• Ca2+ binds in a fast reaction to one of the troponin subunits on the thin filament

• The binding of calcium to the troponin changes it's shape so the myosin binding sites on the actin (thin filament) are exposed

• At rest ATP binds to ATPase head on myosin heads

Muscle contraction

• If no ATP is available the actin myosin complex becomes stable this accounts for the severe rigidity that occurs after death

Innervation (FYI)

• A single nerve fiber and all the muscles it innervates are called a motor unit

• Ca2+ uptake into the terminal causes release of the neurotransmitter acetylcholine (ACh), which has been previously synthesized and stored in synaptic vesicles

Medical Application (FYI)

Myasthenia Gravis• Autoimmune disorder• Progressive weakness caused by a

reduction in the number of functionally active Ach receptors

• In most cases, the first noticeable symptom is weakness of the eye muscles

• http://www.youtube.com/watch?v=BMT4PtXRCVA

Cardiac Muscle

• Heart muscle contains three types of muscle cell which differ in their morphological and/or functional properties:

• (i)   Cells making up the myocardium of the atria and the ventricles, and make up the bulk of the heart; (ii)    rhythmically active self excitatory "pacemaker cells"; and (iii)    cells that make up a network of specialized conducting pathways (Purkinje fibers) that enhance the spread of localized excitation across the rest of the cardiac muscle http://www.youtube.com/watch?v=_gbGA5il4Sg&feature=related

Cardiac Muscle

• Short and branched• Cross striated banding similar to

skeletal muscle• Each muscle cell possesses one or

two centrally located pale nuclei• Endomysium rich in capillary network• Intercalated disks: junctional

complexes between adjacent cardiac muscle cells

• The junctions are straight lines or exhibit a step like pattern

1. Transverse portion runs at right angle to the fibers

2. A lateral portion runs parallel to the myofilaments

Cardiac Muscle

• 3 main functional specializations within the disk

• Fascia adherentes (hemi Z lines) ribbon like structures on the transverse portion of the disk serve as anchoring sites for actin filaments

• Macula adherentes (desmosomes) are also present in the transverse portion and bind cardiac cells together

• Gap junction on the lateral portions of the disk, provide ionic continuity between adjacent cells

Diads of cardiac muscles versus triads of skeletal muscles• Cardiac muscles have diads

rather than triads, and is located in the region of the Z lines rather than the AI junction

• The diad is composed of a single t-tubule paired with a terminal cisterna of the sarcoplasmic reticulum.

Cardiac Muscle

Smooth Muscle

• Elongated fusiform non striated cells

• Single central nucleus• Narrow part and broadest parts

are adjacent for tightest packing• Enclosed by a basal lamina and a

network of reticular fibers• T tubules are not present in the

smooth muscles

Smooth Muscle

Smooth Muscle

• Smooth muscles have intermediate fibers for stabilization of the cytoplasmic architecture: Desmin and Vimentin

• Two types of dense bodies: one membrane associated and one cytoplasmic (similar to Z line of striated muscle)

• Smooth muscles occur in large sheets and have abundant gap junctions

Differences Between MusclesProperties Skeletal Muscle Cardiac Muscle Smooth Muscle

Location Muscles of skeleton Heart Visceral organs

Cell shape Long cylindrical Short branched Fusiform

Nuclei Multiple , peripheral

One or two, central Single, central

Striations Yes Yes No

T tubules and sarcoplasmic reticulum

Triads at A-I junctions

Diads at Z line No T tubules

Cell junctions None Intercalated discs (Adherens, desmosomes and gap junctions)

Gap junctions

Differences Between MusclesProperties Skeletal Muscle Cardiac Muscle Smooth Muscle

Connective tissue Endomysium, perimysium and endomysium

Endomysium, subendocardial and subpericardial CT layers

Endomysium and less organized CT layers

Major locations Skeletal muscles, tongue, diaphragm

Heart Blood vessels, digestive tract, uterus and bladder

Key function Voluntary Involuntary Involuntary

Efferent innervation Motor Autonomic Autonomic

Contractions Triggered at motor end plate

Intrinsic at SAN Partial, slow, often spontaneous

Cell response to increased load

Hypertrophy Hypertrophy Hypertrophy and hyperplasia

Capacity for regeneration

Very poor Very poor Good

Differences Between Muscles

Regeneration of Muscle Tissue

• Cardiac muscle has no regenerative capacity beyond early childhood, damage in cardiac muscle (infarct) is generally replaced by connective tissue forming scars

Regeneration of Muscle Tissue

• In skeletal muscle, the nuclei are not capable of mitosis however the cells can undergo limited generation due to presence of satellite cells

• Satellite cells:1. reside in the basal lamina

surrounding each muscle cell2. Considered to be dormant myoblasts

that proliferate in case of injury3. They are implicated in cell

hypertrophy

Regeneration of Muscle Tissue

• Smooth muscle is capable of active regeneration

• Viable smooth muscle cells undergo mitosis and pericytes from blood vessels undergo mitosis and provide for the replacement of the damaged tissue