#13338 - Skeletal Muscle - Organisation of the Body

Skeletal muscle

Embryological development

-notochord expresses SHH, which stimulates the somites to segregate into sceleretome and dermamyotome

-muscle develops from the myotome from the dermamyotome

-signalling molecule, neurotrophin, wingless family 1,3 from neural tube and ectoderm stimulates the expression of PAX 3 and PAX 7 which stimulates the formation of myoblasts- committed stage

-myoblasts proliferate and fuse to from multinucleate myotubes

-the myotubes are stimulated to express muscle specific proteins- activation of Myf5, MyoD, myogenin

-some of the myoblasts remain attached to the basal lamina- satellite cells

Function of muscle

-produce movement of the joints of the skeleton

-maintain posture

-support soft tissues

-protect anatomical openings

-maintain body temperature via shivering

Sturcture

• The whole muscle, bundles of fascicles, all surrounded by the epimysium- dense connective tissue

• Bundles of myofibres, fascile, that are held together by connective tissue known as permysium.

• Each myofibre is surrounded by the endomysium

• Each myofibre is made up of many myofibrils

• Each myofibrils is made up of an end to end arrangement of sarcomeres that consist of myofilaments arranged as an interdigitating structure of thick and thin filaments which gives skeletal a striated appearance under a microscope . Each sarcomere is a repeating unit between Z disks

Histological appearance of skeletal muscle

• -striated and multinucleate

• -most of the myocyte is stained pink as there are a large number of proteins

• -nuclei is stained purple and is found around the edge of the cell

Ultrastructure

-Thick filaments

• 10nm wide and 1.5 micrometer long

• Myosin- consists of 2 heavy chains- each chain has an alpha helix and a globular head. The alpha helices of the chains are supercoiled to give a rigid rod like tail. The globular heads protrude to form cross bridges. It also consists of 2 light chains that are associated with the globular heads

• The tails of the myosin are arranged in parallel bundles

• Three pairs of heads protrude from the parallel bundles of myosin tails, and are 120 degrees apart and form a structure known as the crown

• The myosin filaments are attached to the M line

-Thin filaments

• 5nm wide and 1micrometer long

• Actin- globular subunits that polymerise into a filamentous structure- F actin. The filamentous strand is made up of 2 alpha helical strands that wrap around each other.

• The actin is bound to the Z line via actin binding proteins: alpha actinin

• The actin is associated with tropomyosin, 2 alpha helices twist around the grooves formed by the actin and they block the myosin binding sites in the actin groove

• Troponin has 3 subunits, troponin T binds to tropomyosin, troponin I binds to actin and troponin binds to Ca ion

-Striation

• Striations are due to banded appearance of dark and light regions

• Isotropic band, is made up of only actin filaments, I bands shorten during contraction

• Anisotropic band- made up of an overlap of both actin and myosin, A length remains unchanged

Muscoskeletal coupline

Intracellular coupling- within the sarcomere

-forces generated within each sarcomere due to the interactions between myosin and actin – cross bridge cycling- shortens the sarcomere as actin are linked to Z lines and generates tension

Cytoskeletal coupling

-arrangement of the sarcomeres in a myofibril allows the coupling of all forces generated in all sarcomeres in one myofibril

-actin binds to Z discs using alpha actinin -Z discs- tether the thin filaments in one myofibril together-

-desmin- connects Z discs between myofibrils

- intermediate filament that links one myofibre to the next by linking one sarcomere to the next within the muscle fibre by connecting the z discs.

-Desmin also connects the Z discs to the subsarcolemmal cytoskeleton, nucleus, mitochondria

-connections maintain the structural and mechanical integrity of cell during contraction and helps in force transmission

-myosin connects to the M line using myomesin protein

-Titin- connectin protein that connects the z line to the M line in the sarcomere. When the sarcomere shortens, the Titin protein which is made up of 244 domains unfolds. When muscle relaxes, the Titin protein refolds and contributes to the passive elasticity of the muscle- returs the sarcomere to orginisal position. Shock absorbing protein

Transmembrane coupling

dystrophin

-links the cytoskeleton of the sarcomere to the sarcolemma

-links actin filaments to a glycoprotein complex (costameres) on the sarcolemma

-allows force to be transmitted from the sarcomere to the membrane

Duchenne muscular dystrophy- fatal X linked denerative disorder- absence of dystrophin protein- no coupling of force generated in the sarcomere to the membrane so leads to muscle weakness- leads to muscle damage- atropy

-possible treatment of gene replacement of dystrophin but dystrophin is too large to fit in viral vectors

Coupling to connective tissue

-endomysium to perimysium to epimysium

-it is via the connective tissue sheath of the epimysium that contractile force generated by muscle groups is exerted onto skeletal structures

Muscle tendon junction

-the dense connective tissue of the epimysium merges with the regular dense connective tissue of the tendon

-tendons are bundles of type 1 collagen fibres that are attached to the bone via an enthesis- at the junction between the flexible collagen in the tendon and the rigid bone tissue cartilage tissue is developed which is mineralised near the bone Tendons have a high tensile strength and concentrate force onto a small area.

-muscles are connected to bones and tendons

Myoblasts generate several different types of skeletal muscle fibres

• Types:as twitch speed increases, reliance on glycolysis, power, and size of motor unit increase, while fatigue time, oxidative capacity, perfusion, and number of mitochondria decrease

  • Type 1/slow twitch/aerobic- small size, low power, high fatigue resistance, high oxidative capacity, large amount of capillaries

  • Type 2a/moderately fast twitch/long-term anaerobic

  • Type 2x/fast twitch/short-term anaerobic- large size, high power, low fatigue resistance, low oxidative capacity but a high glycolytic capacity and low amount of capillaries

  • Type 2b/very fast twitch/very short-term anaerobic

-Type of skeletal muscle fibres is recognised by myosin ATPase- fast twitch muscle fibres have a high concentration of myosin ATPase so is more darkly stained. Slow twitch muscle fibres have a small amount of ATPase so are more lightly stained.

Form and function of muscles

Length of cells determines the degree of shortening

Number of cells determines the maximum power

-parallel fibres allows greatest shortening

-convergent- broad origin- pectoral muscles

-pennate- feather like packs in more power

Excitation

-muscles are innervated to contract by impulses that are carried by the axons of motor neurons. The sarcolemma in contact with the presynaptic nerve terminal is called the motor end plate. The motor neurones release ACH. ACH binds to ionic receptors on the membrane of the myofibre, end plate potential- propagating action potential on the sarcolemma

-Each myofibre is innervated by one axon- the axon of a motor neuron branches near its terminal to innervate few or many individual muscle cell/myofibres

-motor unit- the total number of myofibres that are innervated to contract by one axon. Muscles with a small innervations ratio control fine movements involving small forces. Large innervations ratio control large forces.

-All skeletal muscle is under voluntary or reflex control by motor neurons of the somatic motor system

Excitation contraction coupling

• Action potentials propagate down the membranes of each myofibre and down the tranverse T tubules which carry the action potential deep into the muscle fibre

• The tranverse T tubules are arranged regularly and surround the myofibrils at two points, are at A-I junction of each sarcomere in a myofibril. At these junctions the T tubules are juxtaposed with the sarcoplasmic reticulum and form structures known as a TRIAD

Coordinated contraction occurs as all the myofibrils respond simultaneously to depolarisation- achieved by a system of T tubules which surround each myofibril- permits a wave of depolarisation to spread from the surface of the sarcolemma throughout the cell...

• The action potential in the transverse T tubules cause L type voltage gated calcium ion channels, arranged in a cluster of four, to open. The presence of these channels was shown through Dihydropyridines- which inhibit these channels- used as antihypertensive drugs as they prevent excitation contraction coupling...These channels are mechanically coupled with the ryanidine receptor found in the SR- these channels are inhibited by ryanodie. The opening of the calcium ion channels in the transverse tubules leads to a conformation change with opens the ryanidine receptor- leads to an efflux of calcium ions out of the SR. In the SR, there is a large store of calcium which is bound to calequestrin

• External calcium from the lumen of T tubules is not required for skeletal mscle as contraction persist even when calcium is absent

CONTRACTION

• The large increase in the intracellular concentrations of calcium leads to contraction

• The calcium ions bind to Troponin C inducing a conformational change in the protein. Troponin I moves away from the actin and troponin T displaces tropomyosin. reveals the myosin binding site on the actin filament and allows the globular heads of the myosin to bind with the actin

Cross bridge cycling- the...