Muscle

BIO 408

Histology

Dr. D. L. Daley

Types of Muscle

n Striated Muscle

n Elongate, multinucleate cells that show cross striations and can undergo voluntary contraction

n Cardiac Muscle

n Elongate and branched cells that show cross striations with intercalated disks at sites of end-to-end contact - contractions are involuntary and rhythmic - single nucleus

n Smooth Muscle

n Collections of fusiform cells that show no cross striations - contraction is slow & involuntary - single nucleus

Skeletal Muscle

n During embryonic development, hundreds of myoblasts line up end-to-end fusing with one another to form multinucleate myotubes

n The myotubes produce the contractile elements called myofibrils that are composed of specific arrays of contractile proteins called myofilaments

Skeletal Muscle

n Muscle fibers vary from 10 to 100mm in diameter

n Muscle fibers (cells) are arranged in parallel to one another

n Intervening spaces between fibers houses parallel arrays of continuous capillaries

n Fibers are pink to red in color because of the oxygen binding myoglobin pigments

Muscle Fiber Classification

n Red (Type I, Slow oxidative)

n Rich in myoglobin, small diameter, numerous mitochondria, slower contracting, not very extensive SR, rich vascular supply and rich in oxidative enzymes and low myosin-ATPase content

n White (Type IIA, Fast glycolytic)

n Little myoglobin, larger diameter, few mitochondria, fast contracting, extensive SR, poorer vascular supply and poor in oxidative enzymes but rich in phosphorylases and high anaerobic capacity, large glycogen supply and high myosin-ATPase content

Muscle Fiber Classification

n Intermediate (Type IIB, fast oxidative)

n Rich in myoglobin, smaller diameter, numerous mitochondria,fast contracting, good vascular supply, high oxidative and anaerobic capacity and high myosin-ATPase content

Investments of Skeletal Muscle

n Epimysium - surrounds the entire muscle

n Dense irregular connective tissue

n Perimysium - surrounds bundles (fascicles) of muscle fibers

n Less dense collagenous connective tissue

n Endomysium - Surrounds each muscle fiber

n Reticular fibers

Light Microscopy of Skeletal Muscle

n Long cylindrical multinucleate cells which - nuclei are peripherally located

n Satellite cells with a single nuclei act as regenerative cells - located in shallow depressions on the muscle cell’s surface

n The bundles of contractile protein, myofibrils are aligned precisely with their neighbors in parallel arrays and are responsible for the light and dark banding characteristic of skeletal muscle

Fines Structure of Skeletal Muscle

n Dark bands - A bands (anisotrophic with polarized light (birefrigent)

n Light bands - I bands (isotrophic with polarized light - do not alter polarized light)

n Center of A band - is a pale area - H band

n Bisected by M line

n Each I band is bisected by thin dark line - Z line or disk

n Sarcomere - the region of a myofibril between two successive Z lines - the contractile unit of as muscle

Fines Structure of Skeletal Muscle

n Single muscle fiber contains multiple myofibrils

n Myofibrils are surrounded by a complex internal membrane system

n The cell membrane or sarcolemma contains numerous long tubular extensions - T tubules (transverse tubules)

n These branch and anastomose but usually remain in a single plane

n Hence each sarcomere contains two sets of t tubules - one at each interface between A and I bands

Fines Structure of Skeletal Muscle

n Sarcoplasmic reticulum (SR) - type of smooth endoplasmic reticulum - stores Ca⁺⁺

n Entirely envelope each myofibril with a meshwork

n The SR has dilated terminal cisternae at each A-I junction

n Two of these cisternae are in close apposition to a t tubule forming a triad

n The surface action potential is spread down the t tubules and bring about release of calcium from the terminal cisternae

n Ca⁺⁺ triggers contraction - relaxation is accomplished by removal of calcium from via pumps in the SR

Fines Structure of Skeletal Muscle

n Myofibrils are held in register with one another by intermediate filaments desmin and vimentin

n These filaments secure the periphery of the Z disks of neighboring myofibrils to each other

n Bundles of myofibrils are attached to the cytoplasmic aspect of the sarcolemma by various proteins including dystrophin - binds to actin

n Deep to the sarcolemma and interspersed between the myofibrils are mitochondria (sarcosomes)

Structure of Myofibrils

n EM reveals rod-like thick filaments (myofilaments) - 15 nm in diameter and 1.5 mm long

n Composed of myosin

n Form parallel array and interdigitate thin filaments

n EM also reveals smaller rod-like thin filaments (myofilaments) - 7nm in diameter and 1.0 mm long

n Composed of actin, troponin and tropomyosin

n Originate at the Z lines and project into the two adjacent sarcomeres

Structure of Myofibrils

n M line - hold thick filaments in specific 3d array in middle of the sarcomere

n Myomesin, C protein and others involved

n Titin - form elastic lattice - anchors thick filaments to the z disks

n Z line - holds thin filaments in specific 3d array

n a-actinin - bind thin filaments in parallel arrays

n Two molecules of nebulin, a long non-elastic protein are wrapped around the entire length of each thin filament

Thick Filaments

n Consists of 200 to 300 myosin molecules

n Myosin - 2 headed golf club

n Light meromyosin - rod-like tail

n Heavy meromyosin - two globular heads with short attendant proximal portions of two rod-like polypeptide chains wrapped around each other

Thin Filaments

n Two twisting strands of of F-actin - polymer of g-actin subunits

n The g actin gobular subunits polymerize in the same spatial orientation - gives filament a polarity

n Plus end of the f-actin is bound to the Z line and the minus end extends toward the center of the sarcomere

n Each g-actin has an active site where the head (crossbridge) of myosin binds

Thin Filaments

n Tropomyosin - pencil-shaped, 40nm long

n Occupies the shallow grooves of the double stranded actin helix

n Bound tropomyosin blocks the active sites on actin

n Approximately 25 - 30 nm from the beginning of each tropomyosin is a troponin complex

n Composed of three globular subunits

n TnT - Troponin T - binds complex to tropomyosin

n TnC -Troponin C - binds calcium

n TnI - Troponin I - binds to actin and prevents interaction of actin and myosin head

Sliding Filament Theory

n Muscle contraction is all or none for a single muscle fiber

n The thin filaments slide relative to the thick such that the Z line to Z line distance of individual sarcomeres shortens

Crossbridge Cycle

Motor Innervation of Skeletal Muscle

n A single a-motor neuron whose cell body resides in the ventral horn of the spinal cord synapse with a fixed number of muscle fibers - called a motor unit

n Motor unit sizes vary dramatically from as little as 5 or 10 muscle fibers to as many as 1000 muscle fibers

n Each unit is all or none

Motor Innervation of Skeletal Muscle

n As an a-motor neuron approaches a muscle fiber it looses its myelin sheath and arborizes

n The terminal of each arborized twig becomes dilated and overlies the motor end plate of individual muscle fibers

n The junction are called neuromuscular or myoneural junctions

Myoneural Junction

Cardiac Muscle

n Non-voluntary branching striated muscle of the heart and proximal portions of the pulmonary veins

n Individual cardiac cells vary in size but are on average 15mm in diameter and 80 mm in length

n Single nuclei

n Intercalated disks occur at sites of end-to-end contact

Intercalated Disks

n Specialized end-to-end junctions

n The transverse portions of the junction have fasciae adherentes and desmosomes abound

n Lateral portions are rich with gap junctions

n On the cytoplasmic aspect of the sarcolemma of intercalated disks, thin myofilaments attach to the fasciae adherentes - analogous to z lines in skeletal muscle

n Gap junction function in rapidly spreading the depolarization (excitation) from one cell to another

Smooth Muscle

n Spindle shaped cells, one nucleus, no cross striations and no t tubule system and little SR - not involve in Ca⁺⁺ storage

Types of Muscle

n Striated Muscle

n Elongate, multinucleate cells that show cross striations and can undergo voluntary contraction

n Cardiac Muscle

n Elongate and branched cells that show cross striations with intercalated disks at sites of end-to-end contact - contractions are involuntary and rhythmic - single nucleus

n Smooth Muscle

n Collections of fusiform cells that show no cross striations - contraction is slow & involuntary - single nucleus

Skeletal Muscle

n During embryonic development, hundreds of myoblasts line up end-to-end fusing with one another to form multinucleate myotubes

n The myotubes produce the contractile elements called myofibrils that are composed of specific arrays of contractile proteins called myofilaments

Skeletal Muscle

n Muscle fibers vary from 10 to 100mm in diameter

n Muscle fibers (cells) are arranged in parallel to one another

n Intervening spaces between fibers houses parallel arrays of continuous capillaries

n Fibers are pink to red in color because of the oxygen binding myoglobin pigments

Muscle Fiber Classification

n Red (Type I, Slow oxidative)

n Rich in myoglobin, small diameter, numerous mitochondria, slower contracting, not very extensive SR, rich vascular supply and rich in oxidative enzymes and low myosin-ATPase content

n White (Type IIA, Fast glycolytic)

n Little myoglobin, larger diameter, few mitochondria, fast contracting, extensive SR, poorer vascular supply and poor in oxidative enzymes but rich in phosphorylases and high anaerobic capacity, large glycogen supply and high myosin-ATPase content

Muscle Fiber Classification

n Intermediate (Type IIB, fast oxidative)

n Rich in myoglobin, smaller diameter, numerous mitochondria,fast contracting, good vascular supply, high oxidative and anaerobic capacity and high myosin-ATPase content

Investments of Skeletal Muscle

n Epimysium - surrounds the entire muscle

n Dense irregular connective tissue

n Perimysium - surrounds bundles (fascicles) of muscle fibers

n Less dense collagenous connective tissue

n Endomysium - Surrounds each muscle fiber

n Reticular fibers

Light Microscopy of Skeletal Muscle

n Long cylindrical multinucleate cells which - nuclei are peripherally located

n Satellite cells with a single nuclei act as regenerative cells - located in shallow depressions on the muscle cell’s surface

n The bundles of contractile protein, myofibrils are aligned precisely with their neighbors in parallel arrays and are responsible for the light and dark banding characteristic of skeletal muscle

Fines Structure of Skeletal Muscle

n Dark bands - A bands (anisotrophic with polarized light (birefrigent)

n Light bands - I bands (isotrophic with polarized light - do not alter polarized light)

n Center of A band - is a pale area - H band

n Bisected by M line

n Each I band is bisected by thin dark line - Z line or disk

n Sarcomere - the region of a myofibril between two successive Z lines - the contractile unit of as muscle

Fines Structure of Skeletal Muscle

n Single muscle fiber contains multiple myofibrils

n Myofibrils are surrounded by a complex internal membrane system

n The cell membrane or sarcolemma contains numerous long tubular extensions - T tubules (transverse tubules)

n These branch and anastomose but usually remain in a single plane

n Hence each sarcomere contains two sets of t tubules - one at each interface between A and I bands

Fines Structure of Skeletal Muscle

n Sarcoplasmic reticulum (SR) - type of smooth endoplasmic reticulum - stores Ca++

n Entirely envelope each myofibril with a meshwork

n The SR has dilated terminal cisternae at each A-I junction

n Two of these cisternae are in close apposition to a t tubule forming a triad

n The surface action potential is spread down the t tubules and bring about release of calcium from the terminal cisternae

n Ca++ triggers contraction - relaxation is accomplished by removal of calcium from via pumps in the SR

Fines Structure of Skeletal Muscle

n Myofibrils are held in register with one another by intermediate filaments desmin and vimentin

n These filaments secure the periphery of the Z disks of neighboring myofibrils to each other

n Bundles of myofibrils are attached to the cytoplasmic aspect of the sarcolemma by various proteins including dystrophin - binds to actin

n Deep to the sarcolemma and interspersed between the myofibrils are mitochondria (sarcosomes)

Structure of Myofibrils

n EM reveals rod-like thick filaments (myofilaments) - 15 nm in diameter and 1.5 mm long

n Composed of myosin

n Form parallel array and interdigitate thin filaments

n EM also reveals smaller rod-like thin filaments (myofilaments) - 7nm in diameter and 1.0 mm long

n Composed of actin, troponin and tropomyosin

n Originate at the Z lines and project into the two adjacent sarcomeres

Structure of Myofibrils

n M line - hold thick filaments in specific 3d array in middle of the sarcomere

n Myomesin, C protein and others involved

n Titin - form elastic lattice - anchors thick filaments to the z disks

n Z line - holds thin filaments in specific 3d array

n a-actinin - bind thin filaments in parallel arrays

n Two molecules of nebulin, a long non-elastic protein are wrapped around the entire length of each thin filament

Thick Filaments

n Consists of 200 to 300 myosin molecules

n Myosin - 2 headed golf club

n Light meromyosin - rod-like tail

n Heavy meromyosin - two globular heads with short attendant proximal portions of two rod-like polypeptide chains wrapped around each other

Thin Filaments

n Two twisting strands of of F-actin - polymer of g-actin subunits

n Sarcoplasmic reticulum (SR) - type of smooth endoplasmic reticulum - stores Ca⁺⁺

n Ca⁺⁺ triggers contraction - relaxation is accomplished by removal of calcium from via pumps in the SR

n Spindle shaped cells, one nucleus, no cross striations and no t tubule system and little SR - not involve in Ca⁺⁺ storage