SKELETAL MUSCLE

Dr Ahmad Saleem

Skeletal Muscle Fibre

• Muscle consists a number of muscle fibers lying parallel to one another and held together by connective tissue

• Single skeletal muscle cell is known as a muscle fiber– Functional Unit of Skeletal Muscle– Length varies from few mm to many cm.– Diameter of 10 to 100 micron– Multinucleated – Large, elongated, and cylindrically shaped– Fibers usually extend entire length of muscle– Like other cells , MF contains motochondria,

microsomes and endoplasmic reticulum etc

• Each Muscle Fiber is surrounded by a plasma membrane called SARCOLEMMA.

• Individual MF is enveloped by layer of connective tissue called ENDOMYSIUM ( which lies outside Sarcolemma)

• Several MF are enveloped together by another connective tissue called PERIMYSIUM

• The entire Muscle is covered all round by EPIMYSIUM.

( Sarcolemma—Endomysium– Perimysium– Epimysium)

• Actin forms the major part of thin filaments.– The thin filaments give rise to I- bands– Actin occurs in two forms

• G-Actin ( Globular monomer)– Each molecule contains one molecule of ATP– Molecular weight of about 43000.

• F-Actin ( Globular monomer)– Fibrous, thickness of 6-7 nm, polymerized G-Actin, contains ADP.– Polymerization occurs in presence of Calcium or Magnesium ions.

• Myosin –II

– Found in Thick Filaments

– Mol Weight of about 460,000.

– Chief Actin Binding Constituent.

– Hexamer containing two identical heavy chains and 4 light chains.

• Troponin

– Troponin –C– Can bind an release Calcium Ions.

– Troponin-I– Exerts an inhibitory action over Actin-Myocin interaction

when Troponin C is without Calcium.

– Troponin T– Serves to bind Troponin C and Troponin I subunits with

Tropomyosin-Actin Complex.

(Troponin complex is found only in Striated Muscle)

Muscle

Tendon

Muscle fiber(a singlemuscle cell)

Connectivetissue

Fig. 8-2, p. 255

Structure of Skeletal Muscle

• Myofibrils

– Contractile elements of muscle fiber

– Regular arrangement of thick and thin filaments• Thick filaments – myosin (protein)

• Thin filaments – actin (protein)

– Viewed microscopically myofibril displays alternating dark (the A bands) and light bands (the I bands) giving appearance of striations

– Light bands , Only Actin, Isotropic to polarized light-thus I-Bands.

– Dark bands, Mainly myosin, Anisotropic to polarized light-Thus A-Bands

Musclefiber

Dark A band Light I band

Myofibril

Fig. 8-2, p. 255

A T-tubule (or transverse tubule) is a deep invagination of the sarcolemma, which is the plasma membrane, only found in skeletal and cardiac muscle cells. These invaginations allow depolarization of the membrane to quickly penetrate to the interior of the cell.

Figure 1.3

Structure of Skeletal Muscle

• Sarcomere – Functional unit of skeletal muscle– Found between two Z lines (connects thin filaments of two

adjoining sarcomeres)– Regions of sarcomere

• A band– Made up of thick filaments along with portions of thin filaments

that overlap on both ends of thick filaments• H zone

– Lighter area within middle of A band where thin filaments do not reach

• M line– Extends vertically down middle of A band within center of H

zone• I band

– Consists of remaining portion of thin filaments that do not project into A band

Z line A band I bandPortionof myofibril

M line

Sarcomere

H zone

Thick filamentThin filament

Crossbridges

M line H zone Z line

A band I band

Thick filament Thin filament

Myosin Actin

Fig. 8-2, p. 255

I band A band I band

Cross bridge

Thick filament

Thin filament

Fig. 8-4, p. 256

Myosin

• Component of thick filament• Composed of SIX polypeptide chains, two identical

heavy chains, and four light chains.• The two heavy chains wrap spirally around each other

for form a double helix; however one end of each of these chains is folded into a globular protein mass called the head; the elongated portion is called the tail.

• Tails oriented toward center of filament and globular heads protrude outward at regular intervals– Heads form cross bridges between thick and thin

filaments• Cross bridge has two important sites critical to

contractile process– An actin-binding site– A myosin ATPase (ATP-splitting) site

Cross Bridges in Myosin Filaments•The protruding arms and heads together are called cross-bridges.

•Each cross-bridge is believed to be flexible at two points called hinges.

•One where the arm leaves the body of the myosin fiilament.•Where the two heads attach to the arm.

ATPase activity of Myosin Head

Another feature of myosin head, essential for muscle contraction is that it functions as an ATPase enzyme. This property allows the head to cleave ATP and to use the energy to energize the contraction.

Structure and Arrangement of Myosin Molecules Within Thick Filament

Actin

• Primary structural component of thin filaments

• Spherical in shape

• Thin filament also has two other proteins

– Tropomyosin and troponin

• Each actin molecule has special binding site for attachment with myosin cross bridge

– Binding results in contraction of muscle fiber

The Actin Filament

• The back bone of the actin filament is a double-stranded F-Actin protein molecule.

• Each strand of double F-actin helix is composed of polymerized G-actin molecules.

• Attached to each one of the G-actin molecules is one molecule of ADP. It is believed that these ADP molecules are the active sites on the actin filaments with which the cross-bridges of the myosin filaments interact to cause muscle contraction.

Composition of a Thin Filament

• A pure actin filament without the presence of troponin-tropomyosin complex binds strongly with myosin molecules, in the presence of Magnesium and ATP.

• However if the troponin-tropomyosin complex is added to the actin filament, this binding does not take place.

• Thus the active sites on the normal actin filament of relaxed muscle are inhibited or actually physically covered by the troponin- tropomyosin complex.

• For contraction to take place the inhibitory effect of the T-T complex must itself be inhibbitted.

Actin and myosin are often called contractile proteins. Neither actually contracts.

Actin and myosin are not unique to muscle cells, but are more abundant and more highly

organized in muscle cells.

Large amount of Calcium Ion

• In the presence of large amounts of calcium ions the inhibitory effect of T-T complex is inhibited.

• Calcium ion combines with troponin-C, the Troponin complex undergoes conformational change that moves it deeper into the groove between the two actin strands.

• This uncovers the active sites of the actin , thus allowing the contraction to proceed.

Tropomyosin and Troponin

• Often called regulatory proteins

• Tropomyosin

– Thread-like molecules that lie end to end alongside groove of actin spiral

– In this position, covers actin sites blocking interaction that leads to muscle contraction

• Troponin

– Made of three polypeptide units• One binds to tropomyosin

• One binds to actin

• One can bind with Ca2+

Role of Calcium in Cross-Bridge Formation

Cross-bridge interaction between actin and myosin brings about muscle contraction by

means of the “Sliding Filament Mechanism.”

Walk-Along Theory of Contraction

Outline

Contractile mechanisms

• Sliding filament mechanism (Theory)

– Ca dependence

– Power stroke

– T tubules

– Ca release• Lateral sacs, foot proteins, ryanodine receptors,

dihydropyradine receptors

– Cross bridge cycling• Rigor mortis, relaxation, latent period

Sliding Filament Mechanism

• Increase in Ca2+ starts filament sliding

• Decrease in Ca2+ turns off sliding process

• Thin filaments on each side of sarcomere slide inward over stationary thick filaments toward center of A band during contraction

• As thin filaments slide inward, they pull Z lines closer together

• Sarcomere shortens

Figure 1.5

Fig. 8-9, p. 260

Basic 4 steps

Power Stroke

• Activated cross bridge bends toward center of thick filament, “rowing” in thin filament to which it is attached

• Sarcoplasmic reticulum releases Ca2+ into sarcoplasm

• Myosin heads bind to actin

• Myosin heads swivel toward center of sarcomere (power stroke)

• ATP binds to myosin head and detaches it from actin

Power Stroke

• Hydrolysis of ATP transfers energy to myosin head and reorients it

• Contraction continues if ATP is available and Ca2+

level in sarcoplasm is high

Sliding Filament Mechanism

• All sarcomeres throughout muscle fiber’s length shorten simultaneously

• Contraction is accomplished by thin filaments from opposite sides of each sarcomere sliding closer together between thick filaments

Changes in Banding Pattern During Shortening

Relaxation

• Depends on reuptake of Ca2+ into sarcoplasmic reticulum (SR)

• Acetylcholinesterase breaks down ACh at neuromuscular junction

• Muscle fiber action potential stops

• When local action potential is no longer present, Ca2+ moves back into sarcoplasmic reticulum

Rigor Mortis

• Rigidity caused by loss of all the ATP which is required to cause the separation of the cross-bridges from the actin filament during the relaxation process.

• Thus, several hours after death the muscles of the body go into a state of contracture, called “ Rigor Mortis”, i.e. the muscle contracts and becomes rigid even without action potential.

• The muscle remains in rigor until the muscle proteins are destroyed by autolysis

Terminal button

Acetylcholine-gated cationchannel

Acetylcholine

T tubule

Surface membrane of muscle cell

Lateralsacs ofsarcoplasmicreticulum

TropomyosinTroponin

Cross-bridge binding

Myosin cross bridge

Actin

Fig. 8-12, p. 262

T Tubules and Sarcoplasmic Reticulum

Sarcoplasmic Reticulum

• Modified endoplasmic reticulum

• Consists of fine network of interconnected compartments that surround each myofibril

• Not continuous but encircles myofibril throughout its length

• Segments are wrapped around each A band and each I band

– Ends of segments expand to form saclike regions – lateral sacs (terminal cisternae)

Transverse Tubules

• T tubules

• Run perpendicularly from surface of muscle cell membrane into central portions of the muscle fiber

• Since membrane is continuous with surface membrane – action potential on surface membrane also spreads down into T-tubule

• Spread of action potential down a T tubule triggers release of Ca2+ from sarcoplasmic reticulum into cytosol

Relationship Between T Tubule and Adjacent Lateral Sacs of Sarcoplasmic Reticulum

Outline

• Mechanics

– Tendons

– Twitch

– Motor unit

– Motor unit recruitment

– Fatigue

– Asynchronous recruitment

– Twitch, tetanus, summation

– Muscle length, isometric, isotonic• Tension, origin, insertion

Skeletal Muscle Mechanics

• Muscle consists of groups of muscle fibers bundled together and attached to bones

• Connective tissue covering muscle divides muscle internally into bundles

• Connective tissue extends beyond ends of muscle to form tendons

– Tendons attach muscle to bone

Muscle Contractions

• Contractions of whole muscle can be of varying strength

• Twitch– Brief, weak contraction– Produced from single action potential– Too short and too weak to be useful – Normally does not take place in body

• Two primary factors which can be adjusted to accomplish gradation of whole-muscle tension– Number of muscle fibers contracting within a

muscle– Tension developed by each contracting fiber

Motor Unit Recruitment

• Motor unit– One motor neuron and the muscle fibers it

innervates• Number of muscle fibers varies among different

motor units• Number of muscle fibers per motor unit and number

of motor units per muscle vary widely– Muscles that produce precise, delicate

movements contain fewer fibers per motor unit– Muscles performing powerful, coarsely controlled

movement have larger number of fibers per motor unit

Motor Unit Recruitment

• Asynchronous recruitment of motor units helps delay or prevent fatigue

• Factors influencing extent to which tension can be developed

– Frequency of stimulation

– Length of fiber at onset of contraction

– Extent of fatigue

– Thickness of fiber

Schematic Representation of Motor Units in Skeletal Muscle

Twitch Summation and Tetanus

• Twitch summation

– Results from sustained elevation of cytosolic calcium

• Tetanus

– Occurs if muscle fiber is stimulated so rapidly that it does not have a chance to relax between stimuli

– Contraction is usually three to four times stronger than a single twitch

Summation and Tetanus

Muscle Tension

• Tension is produced internally within sarcomeres

• Tension must be transmitted to bone by means of connective tissue and tendons before bone can be moved (series-elastic component)

• Muscle typically attached to at least two different bones across a joint

– Origin• End of muscle attached to more stationary part of

skeleton

– Insertion• End of muscle attached to skeletal part that moves

Fig. 8-17, p. 268

Types of Contraction

• Two primary types

– Isotonic• Muscle tension remains constant as muscle changes

length

– Isometric • Muscle is prevented from shortening

• Tension develops at constant muscle length

Contraction-Relaxation Steps Requiring ATP

• Splitting of ATP by myosin ATPase provides energy for power stroke of cross bridge

• Binding of fresh molecule of ATP to myosin lets bridge detach from actin filament at end of power stroke so cycle can be repeated

• Active transport of Ca2+ back into sarcoplasmic reticulum during relaxation depends on energy derived from breakdown of ATP

Energy Sources for Contraction

• Transfer of high-energy phosphate from creatine phosphate to ADP

– First energy storehouse tapped at onset of contractile activity

• Oxidative phosphorylation (citric acid cycle and electron transport system

– Takes place within muscle mitochondria if sufficient O2 is present

• Glycolysis

– Supports anaerobic or high-intensity exercise

Muscle Fatigue

• Occurs when exercising muscle can no longer respond to stimulation with same degree of contractile activity

• Defense mechanism that protects muscle from reaching point at which it can no longer produce ATP

• Underlying causes of muscle fatigue are unclear

Central Fatigue

• Occurs when CNS no longer adequately activates motor neurons supplying working muscles

• Often psychologically based

• Mechanisms involved in central fatigue are poorly understood

Outline

• Other types

– Fibers• Fast • slow• Oxidative• glycolytic

– Smooth, cardiac

– Creatine phosphate

– Oxidative phosphorulation• Aerobic, myoglobin

– Glycolysis• Anaerobic, lactic acid

Major Types of Muscle Fibers

• Classified based on differences in ATP hydrolysis and synthesis

• Three major types

– Slow-oxidative (type I) fibers

– Fast-oxidative (type IIa) fibers

– Fast-glycolytic (type IIx) fibers

Characteristics of Skeletal Muscle

Fibers

Control of Motor Movement

• Three levels of input control motor-neuron output

– Input from afferent neurons

– Input from primary motor cortex

– Input from brain stem

Muscle Spindle Structure

• Consist of collections of specialized muscle fibers known as intrafusal fibers

– Lie within spindle-shaped connective tissue capsules parallel to extrafusal fibers

– Each spindle has its own private efferent and afferent nerve supply

– Play key role in stretch reflex

Muscle Spindle Function

Alpha motorneuron axon

Gamma motorneuron axon

Secondary (flower-spray)endings of afferentfibers

Extrafusal (“ordinary”)muscle fibers

Capsule

Intrafusal (spindle)muscle fibers

Contractile end portionsof intrafusal fiber

Noncontractilecentral portionof intrafusalfiber

Primary (annulospiral)endings of afferent fibers

Fig. 8-24, p. 283

Stretch Reflex

• Primary purpose is to resist tendency for passive stretch of extensor muscles by gravitational forces when person is standing upright

• Classic example is patellar tendon, or knee-jerk reflex

Patellar Tendon Reflex

Outline

• Other muscle types

– Smooth, cardiac

– This information is covered in detail in the lecture on the heart.

Smooth Muscle

• Found in walls of hollow organs and tubes

• No striations

– Filaments do not form myofibrils

– Not arranged in sarcomere pattern found in skeletal muscle

• Spindle-shaped cells with single nucleus

• Cells usually arranged in sheets within muscle

• Have dense bodies containing same protein found in Z lines

Smooth Muscle

• Cell has three types of filaments

– Thick myosin filaments• Longer than those in skeletal muscle

– Thin actin filaments• Contain tropomyosin but lack troponin

– Filaments of intermediate size• Do not directly participate in contraction

• Form part of cytoskeletal framework that supports cell shape

Intermediatefilament

Thick filament

Thin filament

Dense body

Fig. 8-28, p. 288

Stepped art

Calcium Activation of Myosin Cross Bridge in Smooth Muscle

Comparison of Role of Calcium In Bringing About Contraction in SmoothMuscle and Skeletal Muscle

Smooth Muscle

• Two major types

– Multiunit smooth muscle

– Single-unit smooth muscle

Multiunit Smooth Muscle

• Neurogenic• Consists of discrete units that function

independently of one another• Units must be separately stimulated by nerves to

contract• Found

– In walls of large blood vessels– In large airways to lungs– In muscle of eye that adjusts lens for near or far

vision– In iris of eye– At base of hair follicles

Single-unit Smooth Muscle

• Self-excitable (does not require nervous stimulation for contraction)

• Also called visceral smooth muscle

• Fibers become excited and contract as single unit

• Cells electrically linked by gap junctions

• Can also be described as a functional syncytium

• Contraction is slow and energy-efficient

– Well suited for forming walls of distensible, hollow organs

Cardiac Muscle

• Found only in walls of heart

• Striated

• Cells are interconnected by gap junctions

• Fibers are joined in branching network

• Innervated by autonomic nervous system