SKELETAL MUSCLE STRUCTURE

Skeletal muscle consists of numerous muscle fibers which are extended the entire length of the muscle. The diameter of single muscle fiber ranges from10 to 80 microns. Muscle fiber is considered as muscle cell and it is multinucleated. Each muscle fiber contains several hundred to several thousand myofibrils. Each muscle fiber is supplied by one nerve ending usually in the middle of the fiber.

The Structure of a Skeletal Muscle Fiber

Sarcolemma (true cell membrane plus surface thin layer that contains thin collagen fibrils) encloses MF and separates it from extracellular space . The surface layer is inserted at the end of the MF into muscle tendon which is attached to the bone. Transverse tubules (Ttubules) open to out side; communicate between out side muscle fiber and interior of the fiber. They are filled by extracellular fluid.

.(The Structure of a Skeletal Muscle Fiber (Cont

***Sarcoplasm (muscle cell cytoplasm(: intracellular fluid surrounds myofibrils and contains high concentration of K+, Mg++ and PO4-3 but

very low Ca++ concentration. It contains also large no. of

mitochondria for formation of ATP needed for muscle contraction. ***Sarcoplasmic reticulum (modified endoplasmic reticulum(. It

is the

source of Ca++ needed for contraction.

Skeletal muscles have striated appearance. This is due to presence of two alternating bands (light one called I and dark one called A bands). These bands are formed by two filaments (thick and thin filaments). These filaments partially interdigitate.

I bands contain thin filaments while A bands contain thick filaments and the ends of thin filament overlapping the thick ones.

Sarcomere: functional unit of striated muscle

Thin filaments are attached to Z line or disc and extended in both direction to interdigitate with thick filaments. The distance between two successive Z line is called SARCOMERE which is the functional unit of skeletal muscle.

H Zone is in the middle of dark band

and it is formed by myosin filaments only

M line in the middle of dark band

***Myosin (thick) filaments are attached to Z line through TITIN filaments which are formed from titin protein. These titin filaments act like springs keeping myosin filaments in their places and return Z lines to their place after shortening and elongation of the sarcomere i.e increases the elasticity of the muscle.

Myosin filaments Z line Actin filaments Actin filaments

1 m
I band A band Sarcomere I band

Changes in the appearance of a Sarcomere during the Contraction of a Skeletal Muscle Fiber

During muscle contractions the thin filaments are pulled by thick ones inwards (towards the center of the sarcomere). The two Z lines are pulled too, decreasing the length of the sarcomere. Also as consequence of the sliding of thin filaments, the I band and H zone become narrower while A band width does not change.

Molecular characteristics of thick filaments

They are formed of myosin molecules. Myosin molecule of 480000 MW have two heavy chains and four light chains The two heavy chains at one end wrap spirally around each other to form tail while the other end folds into globular shape forming the two heads of the molecule. To each head two light chains are attached, The thick filament is made up of 200 myosin molecules. The tails of these molecules form the body of the filament while the heads protrude outward from the body forming the cross-bridges.

The total length of thick filament is 1.6 micrometer. The center of the filament has no cross-bridges heads

The head of myosin molecule has two functional sites: 1. Actin binding site: This site has high tendency to attach to actin molecule 2. ATPase enzyme: This can cleave ATP molecule to produce high energy phosphate bond to energize contraction process

ATPase Actin-binding site

Thin filaments
Thin filament is composed of strands of actin molecules, troponin and tropomyosin molecules. - Actin molecule has MW of 42000 . Attached to each actin molecule one molecule of ADP which acts as site for interaction with myosin head -Troponin complex consists of three subunits: 1. Troponin C- binds with Ca++ 2. Troponin I binds with actin 3. Troponin T binds with tropomyosin -Tropomyosin molecule has MW of 70000 which wrapped spirally around actin strand and at rest covers the myosin binding site on actin molecules. Binding site for attachment with myosin cross bridge

Role of tropomyosin in thin filament

*** Actin in thin filaments has high tendency (affinity( to bind to

myosin. This binding is prevented by tropomyosin-troponin complex. The active sites on actin molecules in thin filaments are covered or inhibited by tropomyosi-troponin complex. In order to make actin to bind with myosin during contraction, the effect of tropomyosi-troponin complex must be removed or inhibited. This can be done by increasing Ca++ concentration in sarcoplasm.

EXCITATION CONTRACTION COUPLING in skeletal muscle THREE STEPS

1
ELECTRICAL EXCITATION i.e Generation of Muscle action potential

2
ELEVATION Of Intracellular ++Ca

3
CONTRACTION i.e Cross bridge cycle movement of thin( Filament on thick (Filament

The net result is movement of Z lines toward each other and therefore the width of sarcomere is decreased.

STEP 1: generation of action potential in muscle fiber

** Muscle fibers are activated by motor nerve fibers which release enough ACh to depolarize the muscle fibers ACh opens cations channels and more Na+ influx occur this will

cause end plate potential ( graded potential ( which leads to generation of action potential.

The action ponential propagates along sarcolemma and travels deep in the muscle fiber through transverse tubules (T-Tubules(. Action potential reaches the sarcoplasmic reticulum which is near to T tubules. Opening of Ca++ channels of sarcoplasmic reticulum

EXCITATION-CONTRACION COUPLING

Step 2: elevation of Ca++ inside muscle fiber

**Opening of Ca++ of sarcoplasmic reticulum leads to movement of large amount of Ca++ into sarcoplasm . Increased intracellular Ca++ initiates cross-bridge cycles and therefore contraction. Ca++ concentration in sarcoplasm increases 500 times.

** Sarcoplasmic

reticulum is considered as Ca++ store and when Ca++ channels open Ca++ moves by diffusion from high concentration in sarcoplasmic reticulum into sarcoplasm where Ca++ levels are very low.

Step 3: cross-bridge cycle movement of thin filaments on thin filaments walk-along theory When Ca++ levels increase inside muscle it binds with troponin C and this causes movement of tropomyosin away from myosin binding sites on actin in thin filament (exposing these sites). This initiates the cross bridge cycles.

The Contraction Cycle

Ca++ conc.is very low, myosin-binding sites are covered by tropomyosintroponin coplex. Myosin heads hydrolyze ATP into ADP and high energy phosphate bond. Heads of myosin are oriented perpendicularly towards thin filament.

Increased Ca++ conc. Binds with troponin C causing displacement of tropomyosin/troponin complex aside and exposing the myosinbinding sites on actin molecules

.(The Contraction Cycle (Cont

Myosin heads attached to actin. This attachement causes conformational changes tilting the heads toward the center. This tilting provides the power stroke to pull the thin filament inward.

The power stroke is energized by phosphate bonds produced previously. With tilting, the ADP and phosphate are released from myosin heads

.(The Contraction Cycle (Cont

New molecules of ATP attach to myosin heads and this causes detachment of the heads from thin filament and heads return to their perpendicular position and attached to new sites on thin filament.

The ATPase enzyme in the head cleaves ATP into ADPand phosphate bond and thus the head of myosin to attach to actin if Ca++ is still high and new cycle of pulling of thin filament toward the center of the sarcomere begins.