05.contraction Of Skeletal Muscle

Chapter 6

Contraction of Skeletal Muscle

Outline Physiological structure of skeletal muscles Mechanism of muscle contraction Energetics of muscular activity Analysis of the force generated by contraction Summation of contraction

§ 6.1 Physiological Structure of Skeletal Muscles

The parts of a muscle Skeletal muscle Muscle fibers Nuclei Cytosole Myofibrils Thick filament Thin filament

Filament

Sarcomere: the basic unit of contraction

Structure of a sarcomere

1. 2. 3. 4. 5.

Actin and myosin filaments(A-band,) Myosin filaments only (H-zone) Actin filaments only (I-band) M line Z line

Myofilament

Molecular Structure of Myofilament Thick filament: Myosin F

Head consists of 4 light, two heavy chain Tail consist of two heavy chains

C

Actin has binding sites of myosin Thin filament F

Tropomyosin R

Trponin has affinities for actin, tropomyosin and Ca2+

Actin binding site ATP binding site

Thin filament

§ 6.2 Mechanism of contraction Sliding filament theory When muscle shorten, the filaments of action and myosin which make up a sarcomere do not shorten; rather they slide past each other like the fingers of two hands interdigitating.

The Molecular Basis of Contraction The Crossbridge Cycle • The crossbridge cycle is the process of the myosin binding to the actin, going through the Power Stroke, and then disengaging from the Actin.

The Crossbridge Cycle Muscle is a chemomechanical transducer. It has the ability to convert chemical energy, stored in the terminal phosphate group of ATP, into mechanical work. The myosin crossbridge, or myosin molecular motor, is the site for this energy conversion. Thus in addition to generating force and shortening, myosin is an enzyme that hydrolyzes ATP (i.e. ATPase).

The energetic of filament sliding 1. During crossbridge cycle, myosin converts the chemical energy of ATP into the mechanical energy of filament sliding. 2. Each cycle of mechanical activity of the myosin crossbridge takes about 50 ms and is accompanied by a cycle of ATPase activity. 3. During a contraction, each myosin head undergoes a conformational change that moves the thin filament 5 to 15 nm during a period as shorter as 50ms.

• Two sarcomeres, or sets of filament arrays, shortening according to the filament sliding hypothesis. The thick filaments (orange) consist of myosin, and the thin filaments (green) consist predominantly of actin.

Biochemical Cycle for ATP Hydrolysis • Hydrolysis occurs while myosin is detached. • Hydrolysis of ATP primes myosin for attachment. • Once attached to actin, the products of ATP hydrolysis are released and the myosin then undergoes a conformational change believed to be the force generating step or powerstroke. • Myosin detaches from actin upon binding of ATP to complete one cycle of the actomyosin ATPase.

§6.3 Energetics of Muscular Activity • A single muscle fiber may contain 15 billion thick filaments • When that muscle fiber is actively contracting, each thick filament breaks down roughly 2500 ATP molecules per second

Energy for Contraction ATPase ADP + Pi + energy 50-70% • ATP myosin • Na/K ATPase, Ca ATPase 10-20, 10-30% • Amount of ATP in muscle is small…. – Must be quickly re-synthesized • Three ATP production lines:

1. Creatine Phosphate 2. Rapid Glycolysis 3. Aerobic Oxidation

Three source of ATP Production

Energy Use and the Level of Muscle Activity

In a resting skeletal muscle • The demand for ATP is low • Resting muscle fibers absorb fatty acids and glucose that are delivered by the bloodstream • The extra ATP is used to build up reserves of Creatine Phosphate (CP) and glycogen

At moderate levels of activity • the demand for ATP increases, of which demand is met by the mitochondria • As the rate of mitochondrial ATP production rises, so does the rate of oxygen consumption. • As all the ATP produced is needed by the muscle fiber, and no surplus is available, the skeletal muscle now relies primarily on the aerobic metabolism of pyruvic acid to generate ATP •

At peak levels of activity • the ATP demands are enormous and mitochondrial ATP production rises to a maximum • At peak levels of exertion, mitochondrial activity can provide only about 1/3 of the ATP needed. • The remainder is produced through glycolysis

The difference of muscle fiber

Motor Unit •One somatic motor unit and the muscle fibers that it innervates

 The number of muscle fibers per motor unit can vary from four to several hundreds  Muscles that control fine movements (fingers, eyes) have small motor units  Large weight-bearing muscles (thighs, hips) have large motor units

Motor Unit

Muscle Tone • Muscle tone: – Is the constant, slightly contracted state of all muscles, which does not produce active movements – Keeps the muscles firm, healthy, and ready to respond to stimulus

• Spinal reflexes account for muscle tone by: – Activating one motor unit and then another – Responding to activation of stretch receptors in muscles and tendons

§6.4 Analysis of the Force Generated by Contraction • Now that you are familiar with the basic mechanisms of muscle contraction at the level of the individual muscle fiber, we can begin to examine the performance of skeletal muscles--organs of the muscular system. In this section, we will consider the coordinated contractions of an entire population of skeletal muscle fibers.

Work Output During Muscle Contraction When a muscle contracts against a load, it performs work. Energy is transferred from muscle to the external load.  How much work has been done by muscle contraction? It defined by: W(work output) ＝ L (load) × D (distance) 　

Isometric Contractions the muscle as a whole does not change length, and the tension produced never exceeds the resistance holding a heavy weight above the ground, pushing against a locked door, or trying to pick up a car These are rather unusual movements. However, many of the reflexive muscle contractions that keep your body upright when you stand or sit involve the isometric contractions of muscles that oppose the force of gravity.

Isometric Contraction •Isometric Contraction = Muscle does not shorten •Tension increases

Isometric Contraction Tension increases to the muscle’s capacity, but the muscle neither shortens nor lengthens Occurs if the load is greater than the tension the muscle is able to develop

 Since D = 0 so, W = 0, that means energy→tension

wall

How can a muscle generate force without changing its length ? • Each muscle elastic elements: – Tendons – Intracellular cytoskeletal proteins with elastic properties – Contractile proteins themselves can stretch

• These are included in the term: series elastic elements.

Tendon

Non-contractile and connective tissue in muscle itself

Isotonic Contraction •Isotonic Contraction = tension does not change •Length shortens

Isotonic Contraction In isotonic contractions, the muscle changes in length (decreasing the angle of the joint) and moves the load Shortening occurs when the tension generated by the cross bridge exceeds forces opposing shortening

W=D× L

D load

Muscle Contraction in Living Body  Normal daily activities therefore involve a combination of isotonic and isometric muscular contractions.  As you sit and read this text, isometric contractions of postural muscles stabilize your vertebrae and maintain your upright position.  When you turn a page, the movements of your arm, forearm, hand, and fingers are mainly produced by isotonic contractions.

Isotonic

Isometric

Walking, and running involve isotonic contractions. Standing up or pushing a heavy objective involve isometric contraction.

Effects of initial length on force contraction of the whole intact muscle 　

Terms about force of contraction • Preload – muscle is allowed to develop tension at a preset length. – Afterload – The afterload is the weight that a muscle lifts during an isotonic contraction, or simply saying, is force against which

the muscle contracts

We need to distinguish between muscle… • passive force (tension), is the force developed

by simply stretching a muscle to different lengths (think of a rubber band), which is determined by preload and the elasticity of the muscle itself. • total forces (tension), the force developed when a muscle is stimulated to contract at different preload • active forces (tension) is the force developed when the muscle contracts, determined by subtracting the passive tension from the total tension, representing the relation between preload and tension generated by contraction.

length

no stimulation 50

25

force transducer

force (tension)

length

0

•

motor

length

no stimulation 50

25

force transducer

0

•

motor

force (tension) passive force

length

supramaximal stimulation length 50

25

force transducer

force (tension)

0

•

motor

total force (active + passive) passive force

length

supramaximal stimulation length 50

25

force transducer

force (tension)

0

•

motor

total force passive force

active force

length

physiological range

force (tension)

total force passive force

active force

length

Obviously…. There is a range limitation to generate a greater active force, optimal preload or optimal initial length

Why ？

The active tension is maximal when there is maximal overlap of thick and thin filaments and maximal cross-bridge

 Effects

of afterload on the contraction of muscle:

Force-Velocity relationship

Three effects of velocity of shortening:

Experiment

–latent period of shortening increases with increasing load.

Stop

– duration of shortening decreases with increasing load.

pivot

Afterload

Tension transducer

Preload

9 5 3

–velocity of shortening decreases with increasing load.

Stretch the muscle to desired length by hanging appropriate weight (preload) from the relaxed muscle. The desired preload is determined for the passive length:force relationship •

a) Place a support beneath the muscle to allow additional weights (afterload) to be added without stretching the muscle. b) Stimulate the muscle electrically. c) Record change in muscle length once muscle generates sufficient force to lift total load (preload + afterload). d) Repeat series for different afterloads

Because: 1. The speed of muscle shortening depends on the speed of cross-bridge cycling. 2. The force developed depends on the number of cross-bridge formed. 3. As the afterload on the muscle increases, the velocity will be decreased because cross-bridge can cycle less rapidly against the higher resistance.

Force–Velocity Curve 1. When the load is very small (the weight of the muscle only), the velocity of shortening is maximal. P0: V=0

4. The larger the load the slower the rate of shortening.

2. When the muscle can no longer overcome the mass attached to it-- P0 is the point where That is the isometric force that this muscle can produce. 3. In all cases, both phases are present (isometric followed by isotonic) hence these are auxotonic twitches.

Afterload & Power POWER = FORCE x VELOCITY

physiological power = strength of muscle contraction x velocity of muscle contraction

P=L× V

1. Muscle fiber can shorten rapidly or develop high forces but not at the same time 2. Peak power occurs at approximately 1/3 maximum shortening velocity.

 Effects

of contractility on the contraction of muscle

Contractility is determined by the level of intracellular Ca2+ , the activity of myosin and ATPase, etc. In vivo, the contractility of the muscle is regulated by hormones, drugs, and some other humoral substances.

§ 6.5 Summation of Contraction

The Frequency of Muscle Stimulation • A twitch is a single stimulus–contraction– relaxation sequence in a muscle fiber. • Twitches vary in duration.

• A single twitch can be divided into a latent period, a contraction phase, and a relaxation phase:

2 ms

15ms

25 ms

Wave Summation • If a second stimulus arrives before the relaxation phase has ended, a second, more powerful contraction occurs. The addition of one twitch to another in this way constitutes the summation of twitched ,or wave summation • The duration of a single twitch determines the maximum time available to produce wave summation

Incomplete Tetanus • If the stimulation continues and the muscle is never allowed to relax completely, tension will rise to a peak. • A muscle producing peak tension during rapid cycles of contraction and relaxation is in incomplete tetanus.

Complete Tetanus • Complete tetanus is obtained by increasing the stimulation rate until the relaxation phase is eliminated

Muscle tetanus offers large force of contraction than single twitch In living body, tetanus is most pattern of muscle contraction resulted from a continually impulse from an axon.

Summary Force Regulation in Muscle • Types and number of motor units recruited – More motor units = greater force – Fast motor units = greater force

• Initial muscle length – “Ideal” length for force generation

• Nature of the motor units neural stimulation – Frequency of stimulation • Simple twitch, summation, and tetanus

• The amount of tension produced by an individual muscle fiber depends solely on the number of pivoting cross-bridges. If a muscle fiber at a given resting length is stimulated to contract, it will always produce the same amount of tension. There is no mechanism to regulate the amount of tension produced in that contraction by changing the number of contracting sarcomeres. When calcium ions are released, they are released from all triads in the muscle fiber. As a result, all the myosin heads within zones of overlap will interact with thin filaments. Thus a muscle fiber is either "ON" (producing as much tension as possible at that resting length) or "OFF" (relaxed). This feature of muscle mechanics is known as the all-or-none principle. The amount of tension produced in the skeletal muscle as a whole is therefore determined by (1) the frequency of stimulation and (2) the number of muscle fibers stimulated

• For example, if a twitch lasts 20 msec (1/50 sec), subsequent stimuli must be separated by less than 20 msec--a stimulation rate of more than 50 stimuli per second. Rather than refer to stimulation rate, we usually use frequency, which is a number per unit time. In this instance, a stimulus frequency of greater than 50 per second produces wave summation, whereas a stimulus frequency below 50 per second will produce individual twitches.

Motor Units and Tension Production • All the muscle fibers controlled by a single motor neuron constitute a motor unit • The size of a motor unit is an indication of how fine the control of movement can be. – muscles of the eye: a motor neuron may control 4–6 muscle fibers – leg muscles, where a single motor neuron may control 1000–2000 muscle fibers

Resistance and Speed of Contraction • You can lift a light object more rapidly than you can lift a heavy one because the resistance and the speed of contraction are inversely related • The heavier the resistance, the longer it takes for the movement to begin, because muscle tension, which increases gradually, must exceed the resistance before shortening can occur

• For each muscle, an optimal combination of tension and speed exists for any given resistance. If you have ever ridden a 10-speed bicycle, you are probably already aware of this fact. When you are cruising along comfortably, your thigh and leg muscles are working at an optimal combination of speed and tension. When you come to a hill, the resistance increases. Your muscles must now develop more tension, and they move more slowly; they are no longer working at optimal efficiency. You then shift to a lower gear. The load on your muscles decreases, the speed increases, and the muscles are once again working efficiently.

Wave Summation and Incomplete Tetanus • A single stimulation produces a single twitch, but twitches in a skeletal muscle do not accomplish anything useful. • All normal activities involve sustained muscle contractions

Muscle Relaxation and the Return to Resting Length • As we noted earlier, there is no active mechanism for muscle fiber elongation. The sarcomeres in a muscle fiber can shorten and develop tension, but the power stroke cannot be reversed to push the Z lines farther apart. After a contraction, a muscle fiber returns to its original length through a combination of elastic forces, opposing muscle contractions, and gravity.

• • • • • • •

Some Interesting facts: Rigor mortis is caused by inavilability of ATP in dead muscles. Without ATP, the myosin cross bridge cannot release from the actin and stays bound until the proteins begin to deteriorate a few hours later. Muscle cramps can be caused by two events both involving unwanted calcium in the sarcomere: a. during exercise accumulation of lactic acid may lower the pH and poison the calcium pump resulting in calcium in the sarcomere even when the muscle is not stimulated. Calcium in the sarcomere means muscle contractions. b. In the absence of exercise cramps can be caused by unbalanced electrolyte concentrations around the neuromuscular junction which may result in depolarization of the sarcolemma even though no impulse arrived along the axon. A torn muscle is exactly that: muscle fibers are torn by hyperextension resulting in cellular damage. Muscle must be immobilized and repair is difficult. Most likely to happen in muscles associated with joints with great latitude of motion such as hip but not elbow. Elbow cannot be hyperextend but hip can. Muscles can also be torn by attempting to lift too much weight.

Spatial Summation • The strength of the response depends on the number of motor units recruited to participate in the contraction. A motor unit is a motor axon and all the muscle fibers innervated by it. It may be one or a few fibers or hundreds. The fewer the fibers, the more delicate the response of the muscle. The CNS can achieve an appropriate response by recruiting the proper sizes and numbers of motor units so you are capable of using the same muscle to lift a pencil or an anchor. The process by which the strength of the response is increased is spatial summation. By summing the contributions of several motor units the contraction strength is increased. The summation is over space, rather than time, in that many motor units separated in space are activated simultaneously. In the laboratory spatial summation is accomplished by increasing the strength of the stimulus.

• When an action potential travels down an axon it goes to all fibers the axon is connected with. There is no way to prevent it from going to all these fibers. Each fiber then will contract maximally, in accord with the all or none principle and the entire motor unit will respond. • The strength of response of the muscle, then depends on how many motor units are involved. The more units, the greater the response.

• When an action potential travels down an axon it goes to all fibers the axon is connected with. There is no way to prevent it from going to all these fibers. Each fiber then will contract maximally, in accord with the all or none principle and the entire motor unit will respond. • The strength of response of the muscle, then depends on how many motor units are involved. The more units, the greater the response.

Temporal Summation •

• •

•

Muscles contraction can also be increased by summation over time. We can represent muscle contraction with a standard graph known as a myogram in which time (X) is plotted against strength of response (Y). Such a graph is produced by a kymograph of physiograph in classical muscle physiology laboratories. Single twitch: A single stimulus applied to the muscle results in a single contraction and relaxation known as a single twitch, or simple twitch. The latent period lasts about 0.01 sec (10 milliseconds) and is the period of time during which Ca++ is released form the cisternae into the sarcomere. It is followed by the contraction phase, which lasts about 40 msec and is when the filaments are sliding past each other. The relaxation period is about 50msec and is the time during which Ca++ is actively transported back out of the sarcomere. The entire response lasts less than 100 milliseconds and is the result of a single stimulus

simple twitch • Muscles are capable of receiving closely spaced stimuli and responding to them. (Unless they are so close they fall in the refractory period which is about 5 msec following the first stimulus.) • If the second stimulus arrived during the contraction phase from the first stimulus the strength of the response is strengthened, i.e. the two are summed and the process is temporal summation (temporal). Temporal summation occurs when individual fibers are stimulated by multiple stimulations separated in time. (Spatial summation is the simultaneous recruitment of additional motor units separated in space.) • If the rate of stimulation is fast enough the muscle cannot relax at all between stimuli and the response is a smooth, strong contraction known as tetany. The strength of contractions during summation and tetany exceeds that of a simple twitch. This is another way to achieve a graded response.

Why study muscle? 

Important in movement of the body •

• • •



Skeletal movement Blood flow (heart and blood vessels) Movement of food through the digestive system Uterine contraction

Muscle disease •



Muscular dystrophy

Muscle provides food • •

Muscle tissue is convert into meat The properties of muscle determine the flavor, tenderness and texture of meat

Weight control

 • • • •

Muscle is very expensive to maintain We need it to help burn excess calories During a diet, muscle is lost very quickly unless an individual exercises to maintain it Use it or loose it is a appropriate for muscle tissue

Outline Physiological anatomy of skeletal muscle Molecular mechanism of muscle contraction Effect of actin and myocin filament overlap on tension developed by contacting muscle