MUSCLE CELLS

are excitable cells. can transmit action potential along their cell membrane. convert chemical energy into a mechanical response

Physiologic Properties of Muscle Cells

IRRITABILITY OR EXCITABILITY

CONDUCTIVITY
CONTRACTILITY

THREE MAJOR TYPES OF MUSCLES

TYPES Striations SKELETAL prominent CARDIAC less prominent SMOOTH none

Location
Shape

begins and ends in a tendon

long, cylindrical multinucleated absent

heart
cylindrical branched mono/binucleated present (Intercalated disc) pacemaker cells syncytial function under involuntary control

hollow organs/eyes
spindle-shaped mononucleated present (unitary) absent (multiunit) pacemaker cells syncytial function (unitary) under involuntary control

Anatomical / functional connections Special features Innervation

makes up the great mass of somatic musculature under voluntary control

Primary Function
generate a force or movement in response to a physiological stimulus by transducing chemical or electrical stimuli into a mechanical response.

STRUCTURE OF SKELETAL MUSCLE

Forms 40% of body weight Locomotion Striated or voluntary Multinucleated

SKELETAL MUSCLE

MUSCLE (Epimysium)

FASCICULUS (Perimysium)

MUSCLE FIBER (Endomysium)

MYOFIBRILS MYOFILAMENTS

SARCOMERE

MUSCLE FIBER

Sarcolemma Consists of an inner plasma membrane and outer collagenous layer Invaginates at numerous points to form T-tubules Carries action potential Sarcoplasm Consists of myofibrils Numerous mitochondriae lying parallel to myofibrils Sarcoplasmic reticulum L-tubules Storage of calcium ions

Skeletal muscle Fasciculus Muscle fibers Myofibrils Myofilaments

 Muscle fiber- 10 to 80 in diameter each is composed of 1000s of myofibrils

Each myofibril is in turn made up of myofilaments

Myofilaments (i) contractile- myosin II, actin (ii) modulatory- tropomyosin, troponin

SARCOMERE

LIGHT MICROSCOPIC STRUCTURE

Cross striations due to alternate dark and light bands Light band- Isotropic band- I band- thin filaments Dark band- Anisotropic band- A band- birefringent H zone- lighter zone in A band Z line- in the center of I band M line- in the center of A band Sarcomere- between two z lines- basic unit of muscle

ULTRASTRUCTURE
Myofilaments- thick & thin filaments Myosin-10 to 14nm wide & 1.6m long 1500 in each myofibril Myosin filament made of around 200molecules of myosin Myosin molecule- composed of 6 polypeptide chains- 2 heavy chains and 4 light chains A tail, an arm and 2 globular heads Arm and head form cross-bridge Two hinges Head has sites for ATP and actin binding

 Actin filament- 7nm wide and 1.0m long Extend on both sides of z-lines F-actin forms a double helix Made of 300 G-actin molecules (MW 42,000) G-actin has active sites for interaction with myosin heads

 Tropomyosin- 40nm length and MW of 70,000. Wrapped around actin helix & covers active sites in resting phase Troponin- made of 3 protein subunits (Tn I, Tn C & Tn T)

OTHER PROTEINS
1) Actinin- binds actin to Z lines 2) Desmin- binds Z lines to the plasma membrane

3) Titin- connects Z lines to M lines and provide scaffolding for sarcomere. Provides elasticity
4) Dystrophin, dystroglycans and sarcoglycans

MUSCLE FIBER

Sarcolemma Consists of an inner plasma membrane and outer collagenous layer Invaginates at numerous points to form T-tubules Carries action potential Sarcoplasm Consists of myofibrils Numerous mitochondriae lying parallel to myofibrils Sarcoplasmic reticulum L-tubules Storage of calcium ions

SARCOTUBULAR SYSTEM
T-tubule- inward extension of sarcolemma opens to exterior contain ECF run transverse to myofibrils transmit action potential L-tubule- sarcoplasmic reticulum run parallel to myofibrils terminate in terminal cisternae stores calcium ions Triads- two terminal cisternae abutting a t-tubule

Action potential

Neuromuscular transmission

End plate potential

Muscle Action potential

Propagation of muscle AP along sarcolemma

AP reaches triad via T-tubule

Depolarisation of T-tubule

Dihydropyridine receptor acts as voltage sensor

Opening of ryanodine receptors

Ca2+ influx from Sarcoplasmic reticulum Into cytoplasm

Binding of Ca2+ to Tn C

Conformational change in troponin and tropomyosin

Exposure of binding sites on actin

Interaction of actin and myosin

contraction

Active pumping of Ca2+ back into sarcoplasmic reticulum

Tropomyosin covers binding sites of actin

relaxation

Muscle Contraction

THEORIES OF CONTRACTION
1) Viscoelastic (new elastic body theory) theory1840s to1920s- muscle acts like a stretched spring contained in a viscous medium. 2) Continuous filament theory- during contraction actin and myosin combine to form a single filament. This undergoes folding and shortening due to thermal agitation or loss of water molecules 3) Sliding filament theory

SLIDING FILAMENT THEORY

1954 by A.F.Huxley and H.E.Huxley independently Two overlapping sets of filaments sliding past each other. Thin filaments at each end of sarcomere move towards center between thick filaments. Globular heads of myosin form cross-bridges with actin monomers- cross-bridge theory

 Huxley (1969)- cross-bridges attach to thin filament pull towards center detach attach further down ratchet theory or walk-along theory

ATP attaches to myosin head

ATP split into ADP+Pi

Myosin head cocks up

Attaches to actin monomer

Head tilts towards arm

Powerstroke Actin is pulled

ADP & Pi released

ATP attaches to head

Head releases from actin

ATP is cleaved To ADP & Pi

Head cocks up

EVENTS DURING MUSCLE CONTRACTION

1. 2. 3. 4. Chemical changes Mechanical changes Thermal changes Electrical changes

Chemical changes
ATP attaches to myosin head splits to ADP+Pi myosin head cocks up attaches to actin power-stroke ADP & Pi discarded new ATP attaches to myosin head myosin head released from actin ATP yields 11.5kcal/mol

Sources of ATP
1. ATP present in sarcoplasm- suffice for 1-2sec 2. Creatine phosphate- suffice for 5-8sec. Lohmans reaction CP+ADP=Creatine+ATP 3. Glycolysis- suffice for 1min 4. Oxidation of cellular foodstuff- for longer periods

Mechanical changes
Isotonic contraction- shortening of muscle but volume remains the same Isometric contraction- no change in the length

Thermal changes
1. Resting heat- A.V.HILL- 300cal/min in 70kg man with 30kg of skeletal muscles. 2. Activation heat- energy required for Ca2+ influx, binding to troponin & pumping out of Ca2+10cal/gm 3. Shortening heat- proportional to amount of shortening 4. Maintenance heat 5. Relaxation heat 6. Recovery heat- restitution of ATP and glycogen

Electrical changes
RMP of -90mv AP moves along sarcolemma Velocity of AP conduction- 5m/sec

MOTOR UNIT
Single nerve fiber with all the muscle fibers it supplies for a motor unit Motor units may contain 2 to few hundred muscle fibers Smaller motor units are associated with muscles of fine movements

MOTOR UNIT
a single motorneuron and the muscle fibers it innervates. the number of muscle fibers varies with each motor unit.
3 6 muscle fibers/motor unit > muscles concerned with fine, graded and precise movement. 120 165 muscle fibers/motor unit > muscles concerned with postural and gross movement.

each spinal motorneuron innervates only one kind of muscle fiber, so that all of the muscle fibers in a motor unit are of the same type.

WORKING MODEL
Muscle consists of 3 components 1. Contractile element 2. Series elastic element- arms of cross-bridges, tendon fibers 3. Parallel elastic element- connective tissue

TYPES OF CONTRACTION
1. Isometric contraction- length remains same whereas tension increases. Eg: pushing the wall 2. Isotonic contraction- tension remains same whereas length changes. Eg: throwing a stone

LENGTH-TENSION RELATIONSHIP
Muscle length is held constant at various lengths. Muscle directly stimulated at many points. Tension developed is measured using transducer. Maximum tension at rest length. When muscle is stretched, passive tension is developed due stretching of elastic elements

 Studied in single muscle fiber using optical diffraction patterns of laser. Tension developed is maximum at 2-2.2 when there is optimum overlap of actin and myosin No tension when muscle is stretched so that there is no overlap of actin & myosin filaments With shorter lengths, tension reduces

FORCE-VELOCITY RELATIONSHIP
Muscle is allowed to contract with various loads attached Isotonic contraction Initial latency is time for activation of contractile machinery Later part of latency is time taken to stretch the SEE As the load increases, velocity decreases

 Rigor mortis:Seen after death State of extreme rigidity Due to fixed interaction between actin & myosin heads ATP is needed to break actin-myosin bond Loss of rigidity after few hours due to proteolysis

Types of skeletal muscle

Red muscle fiber Slow twitch period Extensive blood supply Thinner fiber Plenty of mitochondriae Copious myoglobin Less glycogen and glycolytic enzymes Less ATPase activity Sustained contraction White muscle fiber Fast twitch period Lesser blood supply Thicker fiber Less mitochondria Less myoglobin More glycogen & glycolytic & phosphorylase enzymes Less ATPase activity Short bursts of activity

SLOW TWITCH
Synonyms Velocity of Shortening Twitch Duration Diameter Source of Energy Mitochondria Myoglobin Type I / Oxidative Red muscle Slow / Low Longer (100 ms) Small Oxidative System Abundant Greater

FAST TWITCH
Type II / Glycolytic White muscle Fast / High Shorter (7.5 ms) Large Glycolytic / Phosphagen System Few Few Few Deliver extreme amount of power for a few sec to min. Involved in skilled and fine movements

Capillary Density
Function Examples

Greater
Provide endurance Involved in gross /strong / ustained movement

Characteristics
NERVE Velocity of Shortening Excitability Diameter MUSCLE Number of fiber Fatigability Type I

Motor Unit Classification

Type II Fast / High (very fast) Low Large Many Fast High High Deliver extreme amount of power for a few sec to min. Glycolytic Large

Slow / Low (fast) High Small few

Contraction velocity Moderate Low

Force of unit
Function Metabolic Profile Fiber diameter

low
Provide endurance Oxidative Moderate

ELECTROMYOGRAPHY
During a normal twitch, minute electrical potential is dissipated into surrounding. This can be picked up by surface electrodes on skin. All the motor units do not contract at same time- so the electrical potential is prolonged. Amplitude of 0.5mv & duration of 5-8ms

Electromyograph is a high gain amplifier Skin electrodes or needle electrodes are used Motor unit potentials are displayed on CRO Potential is a sharp spike, usually biphasic Larger the motor-unit potential, larger the motor unit.

 Useful for distinguishing nerve from muscle disease EMGs are obtained at rest, during slight muscle contraction, and during maximal muscle activity Henneman principle Fibrillation- contraction of single muscle cells Fasciculation- contraction of groups of muscle cells supplied by a single axon

PROPERTIES OF SKELETAL MUSCLE

1. EXCITABILITY 2. CONTRACTILITY 3. CONDUCTIVITY

4. TONICITY

I.EXCITABILITY
Def: It is the change in potential and the consequent responses inherent to the tissues, in response to a stimulus. Stimulus: It is the change in the external environment bringing about excitation in an excitable tissue.

TYPES OF STIMULUS
Electrical- commonly used in labs Mechanical Thermal Chemical Electro-magnetic

QUALITY OF STIMULUS
Strength of stimulus- subminimal, minimal (threshold), submaximal, maximal and supramaximal Duration of stimulus

STRENGTH-DURATION CURVE

2R

RHEOBASE
U.T DURATION IN ms

 Rheobase: the minimum strength of the current acting on the muscle for a variable period that can bring about a response. Utilization time: the minimum duration for which a current of rheobase strength is applied to excite an excitable tissue Chronaxie: is defined as the shortest duration of stimulus required to excite a tissue by a current strength equal to twice of rheobase voltage. Chronaxie of a tissue is a definite measure of its excitability.

II.CONTRACTILITY
Def: internal events of the muscle which are manifested by shortening or development of tension or both.

Types of contraction: 1) isotonic contraction 2) isometric contraction

 Muscle-twitch (simple muscle curve): The contraction and relaxation of skeletal muscle in response to a single adequate stimulus
All or None response An individual muscle fiber exhibits contraction of an uniform intensity once their particular threshold has been reached

FACTORS AFFECTING CONTRACTION

a) Strength of stimuli- Quantal summation b) Effect of multiple stimuli: 1)effect of 2 successive stimuli: i) beneficial effect ii) superposition iii) summation 2) more than two stimuli: i) clonus ii) tetanus iii) treppe iv) fatigue c) Effect of temperature

 Super-position
The second contraction develops a greater tension than the first one if the second stimulus is applied before the relaxation is complete in the first one. Availability of more Ca++ Ca ++ from the first contraction is not completely pumped into the SR Second stimulus releases Ca ++ and adds to the remaining Ca ++ from the first contraction

Treppe or Stair case effect After a period of rest, sudden series of stimulation results in a series of contraction that increases in amplitude until a steady state is reached. Due to redistribution of intra cellular Ca ++ / more Ca ++ availability

FATIGUE
Def: it is a decrease in the performance due to continuous and prolonged activity Site of fatigue: CNS is the first site of fatigue even though the muscle itself can undergo fatigue.

Nerve is indefatigable

The Skeletal muscle can be Tetanized Why ?

Changes in excitability of a muscle during contraction relaxation coupling Duration of Skeletal muscle AP = 5 ms The muscle like nerve has ARP RRP Supra normal period long negative AP during which the muscle is hyper excitable

Effect of load on muscle contraction 1. Free-load 2. After-load Effect of temperature on muscle contraction 1. Heat rigor 2. Cold rigor 3. Calcium rigor 4. Rigor mortis

III. CONDUCTIVITY
velocity of action potential conduction across skeletal muscle is 5m/sec in nerves it is up to 120m/sec conduction is along the sarcolemma and moves along the T-tubules

IV.TONICITY
Def: it is the state of partial contraction of the muscle Reflex phenomenon Resistance encountered on passive stretching of muscle Rigidity Spasticity