Lec # 2Skeletal Muscle Contraction-1 Date: 17th January, 2012 Time : 9-00 AM – 10-00 AM
Objectives.. 1. explain the process of muscle contraction & relaxation• Mechanism of muscle 2. explain the characteristics of contraction & muscle contraction-muscle relaxation twitch, graded response, summation, clonus, tetanus & fatigue and associate them to• Characteristics real conditions in health & of whole muscle disease contraction 3. explain the length- tension relationship in whole muscle• Remodelling of muscle to match 4. describe remodelling of muscle to function match function
1. Muscle cells are excited by somatic efferent neurons.2. Muscle cell excitation (the muscle cell action potential) triggers muscle cell activity (contraction).3. Calcium (Ca++) is the second messenger that links excitation to contraction
Excitation-Contraction Coupling A term coined in 1952 to describe thephysiological process of converting an electrical stimulus to a mechanical response This process is fundamental to muscle physiology, whereby the electrical stimulus isusually an action potential and the mechanical response is contraction. EC coupling can be dysregulated in many disease conditions.
TRIAD MITOCHONDRIA TERMINAL T- TUBULE CISTERNAE THIN MYOFILAMENT THICK MYOFILAMENT MYOFIBRIL Z M Z
Neuromuscular Transmission T-tubules DIHYDROPYRIDINE RECEPTORS Voltage dependent Ca+2 channelsIn humans, the gene encoding RyR1 SRis located on chromosome 19q13.2 RYANODINE RECEPTORS[RyR1]and spans 104 exons. Voltage dependent Ca+2 channels Opening Ca2+ released from the sarcoplasmic reticulum binds causes flow of Ca2+ from the sarcoplasmic reticulum, after its to Troponin C on actin filaments, release from the Calsequestrin, into the cytoplasm.
• Mutations in the RYR1 gene underlie several debilitating and/or life-threatening muscle diseases including – malignant hyperthermia (MH) , – heat/exercise induced exertional rhabdomyolysis , – atypical periodic paralyses (APP)
1 - Calcium released from sarcoplasmic reticulum2 - Myosin head energized via myosin-ATPase activity which converts thebound ATP to ADP + Pi3 - Calcium binds to troponin4 - Tropomyosin translocates touncover the cross-bridge binding sites
5 - The energized myosin binding sitesapproach the binding sites6 - The first myosin head binds to actin7 - The bound myosin head releasesADP + Pi, flips and the muscle shortens8 - The second myosin head binds toactin
9 - The first myosin head binds ATP to allow the actin and myosin to unbind10 - The second myosin head releases its ADP + Pi, flips & the muscle shortens further11 - The second myosin head binds to ATP to allow the actin and myosin to unbind12 - The second myosin head unbinds from the actin, flips back and is ready for the next cycle
13 - The cross-bridge cycle is terminated by the loss of calcium from the troponin14 - Tropomyosin translocates to coverthe cross-bridge binding sites15 - The calcium returns to thesarcoplasmic reticulum, the musclerelaxes & returns to the resting state
As a muscle shortens, the following is observed:a) sarcomeres shorten;b) A band length remains constantc) I band length becomes shortend) myofilament lengths remain constant
SOME FACTS……….• A single cycle of attachment, swivel, and detachment of the myosin head will produce a linear translation of the myofilaments of about 10 nm.• If all cross-bridges in a myofibril cycle once synchronously, a relative movement equal to about 1% of the muscle length will occur, but obviously muscles shorten by more than 1%.
• The total shortening of a sarcomere during contraction may exceed 1,000 nm; therefore the relative movement of a thin and thick filament would be half this amount or 500 nm.• To achieve this magnitude of change in total length when each cross-bridge cycle produces a 10-nm shortening, a minimum of 50 cycles must occur.
• The flexor muscles of the human upper arm can contract at the rate of 8 m/sec (Wilkie DR: J Physiol (Lond) 110:249-280, 1949), during which they can shorten by as much as 10 cm. This contraction rate gives a contraction rate for the sarcomere of 160 nm/msec. If a stroke of the cross- bridge is taken to be 10 nm, then at this rate there will be a minimum of 16 strokes/msec. Thus, the swivel time for the cross-bridge must be of the order of 60 sec.
• In any case, it is clear that the swiveling of the cross-bridge must be a fast mechanical process.• The cross-bridge theory says that sliding is produced by physical attachment of myosin heads to actin and by rotation of the heads.
• Tension is developed by physical bonds between thick and thin filaments.• Tension depends upon the degree of overlap between thick and thin filaments.• The cross-bridge originates at the thick filament and terminates at the thin filament.
Malignant Hyperthermia• MH is an autosomal dominant disease in which genetically susceptible individuals respond to inhalation anesthetics (e.g., halothane) and muscle relaxants (e.g., succinylcholine) with sustained muscle contractions.• More than 150 different point mutations in the RYR1 gene have been identified and linked to MH .• The majority of RyR1 mutations linked to MH cluster in the cytoplasmic domains of RyR1 (amino acids 35 to 614 and 2129 to 2458).• Another cluster of mutations is found near the carboxyl terminus (4637 to 4973)
• MH is often a silent disorder that goes undetected until the patient undergoes surgery or is exposed to high ambient temperatures (∼37° . The underlying C) physiological consequence of MH is abnormal calcium homeostasis with increase sensitivity of channel opening in response to activators .• An MH episode is characterized by elevations in body temperature, metabolic acidosis, hypoxia, tachycardia, skeletal muscle rigidity, and rhabdomyolysis and is life threatening if not immediately treated with dantrolene
Factors that Affect the Efficiency of Muscle Contraction
Tension and LoadThe force exerted on an object by acontracting muscle is known as tension.The force exerted on the muscle by anobject (usually its weight) is termedload.According to the time of effect exertedby the loads on the muscle contractionthe load was divided into two forms,preload and afterload.
PreloadPreload is a load on the muscle beforemuscle contraction. Determines the initial length of the muscle before contraction.Initial length is the length of the musclefiber before its contraction. It is positively proportional to the preload.
AfterloadAfterload is a load on the muscle after thebeginning of muscle contraction. The reverse force that oppose the contractile force caused by muscle contraction.The afterload does not change the initiallength of the muscle, But it can prevent muscle from shortening because a part of force developed by contraction is used to overcome the afterload.
The Effect of Sarcomere Length on Tension The Length – Tension Curve Concept of optimal length
Types of Contractions ITwitch: a brief mechanical contractionof a single fiber produced by a singleaction potential at low frequencystimulation is known as single twitch.Tetanus: It means a summation oftwitches that occurs at high frequencystimulation
Types of Contractions (II)Afterload on muscle is resistanceIsometric Length of muscle remains constant. Peak tension produced. Does not involve movementIsotonic Length of muscle changes. Tension fairly constant. Involves movement at jointsResistance and speed of contraction inverselyrelated
LECTURE# 3 MUSCLE CONTRACTION-2 DATE: 17TH JANUARY,2012 Time : 10-30 AM to 11-30 AM Venue- LT @ level 1 Sarmishtha Ghosh email@example.com
LEARNING OBJECTIVES Whole body contractions Muscle fiber types Muscle Tone- definition, basis and importance in posture Applied terms: atrophy, hypertrophy,hypotonia, hypertonia, denervation hypersensitivityALSO MAKE SURE YOU ARE AWARE OFHYPOCALCEMIC TETANYTETANUSMALIGNANT HYPERTHERMIA
Skeletal muscle Specialized contractile elements, 80% of the muscle fiber, Dm= 1µm 40% of the ,L=2.5 ft Highly organized body weight cytoskeletal elementsSingle muscle cell SINGLE: multiple nucleiAbundant Large,mitochondria elongated cylinder shaped Dm= 10-100 µm L=2.5 ft
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).
Muscle metabolism- production of energyThree ways • Short duration Creatine-Phosphate exercises system – From Creatine – Sprint <= 10 Phosphate sec. – By Anerobic Anerobic Cellular • Activities lasting pyruvate- lactate Respiration < 10 mins system – By Aerobic Cellular • Activities lasting Respiration > 10 mins Aerobic system
IN THE BODY…..• GROUPS OF MUSCLE FIBERS ARE ORGANIZED AS WHOLE MUSCLES• BUNDLED TOGETHER AND ATTACHED TO BONES• TENDONS- tough collagenous structures CONNECT MUSCLES TO BONES• MUSCLES, BONES & TENDONS – SERVE AS A UNIT
• Contraction of whole muscles can be of varying strength – Number of muscle fibers contracting within a muscle • Motor units and their recruitment – Tension developed by each contracting fiber • Frequency of stimulation • Length of fiber at onset of contraction • Extent of fatigue • Thickness of fiber
• When a weak signal is sent by the CNS to contract a muscle, – the smaller motor units, being more excitable than the larger ones, are stimulated first.• As the strength of the signal increases, – more motor units are excited in addition to larger ones, with the largest motor units having as much as 50 times the contractile strength as the smaller ones. – As more and larger motor units are activated, the force of muscle contraction becomes progressively stronger.• A concept known as the size principle allows for a gradation of muscle force during weak contraction to occur in small steps, which then become progressively larger when greater amounts of force are required.
Classification of voluntary muscular contractions• Voluntary muscular contractions can be classified according to either length changes or force levels.• In concentric contraction, the force generated is sufficient to overcome the resistance, and the muscle shortens as it contracts. This is what most people think of as a muscle contraction.• In eccentric contraction, the force generated is insufficient to overcome the external load on the muscle and the muscle fibers lengthen as they contract. An eccentric contraction is used as a means of decelerating a body part or object, or lowering a load gently rather than letting it drop.• In isometric contraction, the muscle remains the same length. An example would be holding an object up without moving it; the muscular force precisely matches the load, and no movement results.• In isotonic contraction, the tension in the muscle remains constant despite a change in muscle length. This can occur only when a muscles maximal force of contraction exceeds the total load on the muscle.• In isovelocity contraction, the muscle contraction velocity remains constant, while force is allowed to vary. True isovelocity contractions are rare in the body, and are primarily an analysis method used in experiments on isolated muscles which have been dissected out of the organism.
Types of Contraction• ISOTONIC – Muscle tension remains constant while muscle changes length – Body movements, moving external objects• ISOMETRIC – Length remains same while tension increases – Lifting objects heavier than one’s capacity• Shift between isometric and isotonic contractions YOU PICK UP A BOOK TO READLifting the book – biceps : isotonic contraction Hold the book in front of you : isometric contraction
ISOTONIC CONCENTRIC ECCENTRICTENSION REMAINS SAME TENSION REMAINS SAME LENGTH SHORTENS LENGTH INCREASES LOWERING THE LOAD TO THE GROUND
OTHERS…….• Not limited to pure Isotonic & pure Isometric Contractions• Muscle length & Stretch the Bow tension can vary Tension of Biceps throughout a range continuously increases, of motion Bow is drawn further back Length shortens simultaneously
Still More…..• Muscles of tongue – Not attached at the free end – Isotonic contractions : facilitate speech and eating• External eye muscles – Skull @ origin, eye @ insertion – Isotonic : Eye movements• Sphincters : – Unattached to bone – Actually prevents movement – Prevents exit of urine and feces by isotonic contraction
• Velocity of shortening is related to the load• Greater the load, lower is the velocity• Muscles do work in physical sense when it moves an object Work= Force x Distance Muscle tension reqd Through which the To overcome Object is moved The weight of object To be moved Isometric: Isotonic: no object is moved object is moved Mechanical Mechanical Efficiency=0 Efficiency=25% MaintainBody Temperature Heat=100% Heat= 75%
TYPES OF SKELETAL MUSCLE FIBERS• SLOW OXIDATIVE TYPE- I• FAST OXIDATIVE- TYPE-IIa GLYCOLYTIC• FAST GLYCOLYTIC TYPE- IIb
Characteristics• Myosin ATPase activity• Speed of contraction• Resistance to fatigue• Capacity for oxidative phosphorylation• Enzymes for Anerobic Glycolysis• Mitochondria• Capillaries• Myoglobin content• Glycogen content• Content of Sarcoplasmic Reticulum• Fiber diameter• Color of fiber
Type I fibers -also called slow oxidative (SO) fibersPosturalmuscles
Type IIa or fast oxidative-glycolytic(FOG) :a hybrid of FG and SO fibers
Type IIb: fast-twitch glycolytic fibers, also called FG or : most common fast-twitch fibers in humans [ white fibers]
SKELETAL MUSCLE FIBERS SLOW FIBERS FAST FIBERS PROLONGED TENSION RAPID TENSION GENERATOR GENERATOR Large fCSA Small fCSA High inn. ratioLow inn. ratio Can generate small Can generate larger forces@ low metabolic forces@ high metabolic cost cost Aerobic + Mitochondria Anerobic Fatigue Myoglobin Fatigability Resistant Intermediate- Low Tonic Slow twitch multiterminal Single terminal 2A 2B 2X Extraocular m. Postural m. Arm muscles/ other sites.
• Majority of muscles are of mixed fiber type composition being a combination of fast and slow fibers occurring in two arrangements – 1) mosaic - fast and slow fibers uniformly distributed – 2) compartmentalized - fiber types non- uniformly distributed into intramuscular compartments• Some muscles which are used for repetitive or constant tasks (e.g., posture) can be comprised nearly entirely of slow fibers – - e.g., soleus
• Genetic Endowment of muscle fiber types• Adaptation to demands placed on them – Changes in their ATP synthesizing machinery – Changes in their diameter
• Anerobic, short duration,high intensity resistance training – Weight lifting – Muscle enlargement • Actual increase in diameter of fast glycolytic fibers • Increased synthesis of Actin and Myosin filaments – Hypertrophy –• Actions of Testosterone – the male sex hormone• Interconversion between fast muscle fiber types – No conversion between fast and slow fibers• Limited repair system available – No mitosis – Some myoblasts may fuse and cause a muscle fiber – Extensive injury- not adequate
MUSCLE INJURY & REPAIRTriggers a sequence of events that begin with a host inflammatory response that is followed by muscle fiberregeneration and new collagen synthesis.The inflammatory response involves at least three types of cells, including neutrophils, ED1+ macrophages, and ED2+ macrophages.Growth factors and cytokines appear to play a role in the inflammatory processand repair of the damaged tissue.. Satellite cells play an integral role in normal development of skeletal muscle by providing a source for postmitotic myonuclei. In addition, the satellite cell is essential to the repair of injured muscle by serving as a source of myoblasts for fiber regenerationAt the same time muscle fiber regeneration is occurring, there is expression of types I and III collagen that under certain circumstances can lead to scarring and fibrosis.
skeletal-muscle pump• The is the pumping effect of skeletal muscle on veins to increase blood flow. During exercise, muscles squeeze veins, effectively pumping blood back to the heart. This is a significant factor affecting venous return which is the amount of blood that returns to the heart via the veins.• Skeletal muscle surrounding a vein is relaxed, – the upper and lower vein valves are closed – backflow of the blood inside the vein prevented
MUSCLE TONE• Residual muscle tension or tonus• is the continuous and passive partial contraction of the muscles.• helps maintain posture, and it declines during REM sleep.
• Unconscious nerve impulses maintain the muscles in a partially contracted state. If a sudden pull or stretch occurs, the body responds by automatically increasing the muscles tension, a reflex which helps guard against danger as well as helping to maintain balance.• The presence of near-continuous innervation makes it clear that tonus describes a "default" or "steady state" condition. There is, for the most part, no actual "rest state" insofar as activation is concerned.• In terms of skeletal muscle, both the extensor and flexor muscles, under normal innervation, maintain a constant tone while "at rest" that maintains a normal posture.
Pathological tonus• Physical disorders can result in – abnormally low (hypotonia) or – high (hypertonia) muscle tone.• Another form of hypertonia is paratonia, which is associated with dementia. Hypotonia is caused by lower motor neuron disease like poliomyelitis. Hypertonia is caused in upper motor neuron disease like lesion in pyramidal tract and extrapyramidal tract. Hypertonia can be of clasp knife variety, in which there is increased resistance only at the beginning or at the end of the movement, or lead pipe variety, in which there is resistance throughout to passive movement, or it may be of cog wheel type, in which the resistance to passive movement is in jerky manner.•
alpha-gamma coactivation;when we actively contractextrafusal fibers (muscle),the contractile portion ofintrafusal fibers contractas well; this stretches thespindles causing them tofire. Alpha motor neuronsfire to contract extrafusalfibers and gamma motorneurons areCOACTIVATED to firewith alphas to contractintrafusal fiberssimultaneousely
Activation of Stretching of muscles Sensory Neuron Stimulation of MUSCLE SPINDLE MUSCLEOPPOSES Information Processing Contraction At Of Activation of Motor neuron Muscle Motor neuron extrafusal fibers, rich in contractile proteins,
DENERVATION HYPERSENSITIVITY• Innervated adult skeletal muscle is sensitive to acetylcholine at the end-plate region only. After denervation the entire muscle membrane becomes chemosensitive..• The motor nerve to skeletal muscle is cut and allowed to degenerate --------the muscle gradually becomes extremely sensitive to acetylcholine.• This denervation hypersensitivity or supersensitivity is also seen in smooth muscle. Smooth muscle, unlike skeletal muscle, does not atrophy when denervated, but it becomes hyperresponsive to the chemical mediator that normally activates it• It appears that the new receptors are released into the muscle surface from post-Golgi vesicles, giving rise to local ‘hot spots’ in A Ch sensitivity. Their generation appears to be triggered by the absence of a neural factor controlling genetic expression in the muscle cell — this factor may be A Ch itself.
ELECTROMYOGRAM • Diagnose conditions that damage muscle tissue, nerves, or the junctions between nerve and muscle (neuromuscular junctions), for example, a herniated disc. • Evaluate the cause of weakness, paralysis, involuntary muscle twitching, or other symptoms. • Problems in a muscle, the nerves supplying a muscle, the spinal cord, or the area of the brain that controls a muscle can all cause these kinds of symptoms.
• Nerve conduction velocity is often used along with an EMG to differentiate a nerve disorder from a muscle disorder.• NCV detects a problem with the nerve whereas an EMG detects whether the muscle is functioning properly in response to the nerves stimulus.• Nerve conduction studies are done to… – Detect and evaluate damage to the peripheral nervous system, which includes all the nerves that lead away from the brain and spinal cord and the smaller nerves that branch out from those nerves. – Nerve conduction studies are often used to help diagnose nerve disorders, such as carpal tunnel syndrome. – Identify the location of abnormal sensations, such as numbness, tingling, or pain