Chapter 9 - Muscles and Muscle Tissue

Three Types of Muscle Tissue 1 Skeletal muscle tissue: Attached to bones and skin

Striated Voluntary (i.e., conscious control) Powerful Primary topic of this chapter Cardiac muscle tissue: Only in the heart Striated Involuntary More details in Chapter 18 Smooth muscle tissue: In the walls of hollow organs, e.g., stomach, urinary bladder, and airways Not striated Involuntary More details later in this chapter

Special Characteristics of Muscle Tissue Excitability (responsiveness or irritability): ability to receive and respond to stimuli

Contractility: ability to shorten when stimulated Extensibility: ability to be stretched Elasticity: ability to recoil to resting length

Muscle Functions 1 Movement of bones or fluids (e.g., blood) 2 Maintaining posture and body position 3 Stabilizing joints 4 Heat generation (especially skeletal muscle) Skeletal Muscle Each muscle is served by one artery, one nerve, and one or more veins Connective tissue sheaths of skeletal muscle: Epimysium: dense regular connective tissue surrounding entire muscle Perimysium: fibrous connective tissue surrounding fascicles (groups of muscle fibers) Endomysium: fine areolar connective tissue surrounding each muscle fiber Skeletal Muscle: Attachments Muscles attach:

Directlyepimysium of muscle is fused to the periosteum of bone or perichondrium of cartilage

Indirectlyconnective tissue wrappings extend beyond the muscle as a ropelike tendon or sheetlike aponeurosis

Microscopic Anatomy of a Skeletal Muscle Fiber Cylindrical cell 10 to 100 m in diameter, up to 30 cm long

Multiple peripheral nuclei Many mitochondria Glycosomes for glycogen storage, myoglobin for O2 storage Also contain myofibrils, sarcoplasmic reticulum, and T tubules Ultrastructure of Thin Filament Twisted double strand of fibrous protein F actin F actin consists of G (globular) actin subunits G actin bears active sites for myosin head attachment during contraction Tropomyosin and troponin: regulatory proteins bound to actin Sarcoplasmic Reticulum (SR) Network of smooth endoplasmic reticulum surrounding each myofibril Pairs of terminal cisternae form perpendicular cross channels Functions in the regulation of intracellular 2+ Ca levels T Tubules Continuous with the sarcolemma

Myofibrils Densely packed, rodlike elements

~80% of cell volume

Exhibit striations: perfectly aligned repeating series of dark A bands and light I bands Sarcomere Smallest contractile unit (functional unit) of a muscle fiber The region of a myofibril between two successive Z discs Composed of thick and thin myofilaments made of contractile proteins Features of a Sarcomere Thick filaments: run the entire length of an A band Thin filaments: run the length of the I band and partway into the A band Z disc: coin-shaped sheet of proteins that anchors the thin filaments and connects myofibrils to one another H zone: lighter midregion where filaments do not overlap M line: line of protein myomesin that holds adjacent thick filaments together Ultrastructure of Thick Filament Composed of the protein myosin Myosin tails contain: 2 interwoven, heavy polypeptide chains Myosin heads contain: 2 smaller, light polypeptide chains that act as cross bridges during contraction Binding sites for actin of thin filaments Binding sites for ATP ATPase enzymes

Penetrate the cells interior at each A band I band junction Associate with the paired terminal cisternae to form triads that encircle each sarcomere Triad Relationships T tubules conduct impulses deep into muscle fiber Integral proteins protrude into the intermembrane space from T tubule and SR cisternae membranes T tubule proteins: voltage sensors

SR foot proteins: gated channels that regulate Ca2+ release from the SR cisternae

Contraction The generation of force

Does not necessarily cause shortening of the fiber

Shortening occurs when tension generated by cross bridges on the thin filaments exceeds forces opposing shortening Sliding Filament Model of Contraction In the relaxed state, thin and thick filaments overlap only slightly

During contraction, myosin heads bind to actin, detach, and bind again, to propel the thin filaments toward the M line As H zones shorten and disappear, sarcomeres shorten, muscle cells shorten, and the whole muscle shortens Requirements for Skeletal Muscle Contraction 1 Activation: neural stimulation at a neuromuscular junction 2 Excitation-contraction coupling: Generation and propagation of an action potential along the sarcolemma

Final trigger: a brief rise in intracellular Ca2+ levels

Events at the Neuromuscular Junction Skeletal muscles are stimulated by somatic motor neurons

Axons of motor neurons travel from the central nervous system via nerves to skeletal muscles Each axon forms several branches as it enters a muscle Each axon ending forms a neuromuscular junction with a single muscle fiber

Neuromuscular Junction Situated midway along the length of a muscle fiber

Axon terminal and muscle fiber are separated by a gel-filled space called the synaptic cleft Synaptic vesicles of axon terminal contain the neurotransmitter acetylcholine (ACh) Junctional folds of the sarcolemma contain ACh receptors

Events at the Neuromuscular Junction Nerve impulse arrives at axon terminal

ACh is released and binds with receptors on the sarcolemma Electrical events lead to the generation of an action potential

Destruction of Acetylcholine ACh effects are quickly terminated by the enzyme acetylcholinesterase

Prevents continued muscle fiber contraction in the absence of additional stimulation

Events in Generation of an Action Potential 1 Local depolarization (end plate potential): ACh binding opens chemically (ligand) gated ion channels

Simultaneous diffusion of Na+ (inward) and K+ (outward)

More Na+ diffuses, so the interior of the sarcolemma becomes less negative Local depolarization end plate potential Generation and propagation of an action potential: End plate potential spreads to adjacent membrane areas Voltage-gated Na+ channels open Na+ influx decreases the membrane voltage toward a critical threshold If threshold is reached, an action potential is generated

Local depolarization wave continues to spread, changing the permeability of the sarcolemma Voltage-regulated Na+ channels open in the adjacent patch, causing it to depolarize to threshold Repolarization: Na+ channels close and voltage-gated K+ channels open K+ efflux rapidly restores the resting polarity Fiber cannot be stimulated and is in a refractory period until repolarization is complete Ionic conditions of the resting state are restored by the Na+-K+ pump

Excitation-Contraction (E-C) Coupling Sequence of events by which transmission of an AP along the sarcolemma leads to sliding of the myofilaments Latent period:

Time when E-C coupling events occur Time between AP initiation and the beginning of contraction AP is propagated along sarcomere to T tubules Voltage-sensitive proteins stimulate Ca2+ release from SR Ca2+ is necessary for contraction

Role of Calcium (Ca2+) in Contraction At low intracellular Ca2+ concentration:

Tropomyosin blocks the active sites on actin Myosin heads cannot attach to actin Muscle fiber relaxes At higher intracellular Ca2+ concentrations: Ca2+ binds to troponin Troponin changes shape and moves tropomyosin away from active sites Events of the cross bridge cycle occur When nervous stimulation ceases, Ca2+ is pumped back into the SR and contraction ends

Cross Bridge Cycle Continues as long as the Ca2+ signal and adequate ATP are present

Cross bridge formationhigh-energy myosin head attaches to thin filament Working (power) strokemyosin head pivots and pulls thin filament toward M line Cross bridge detachmentATP attaches to myosin head and the cross bridge detaches

Cocking of the myosin headenergy from hydrolysis of ATP cocks the myosin head into the highenergy state Review Principles of Muscle Mechanics 1 Same principles apply to contraction of a single fiber and a whole muscle 2 Contraction produces tension, the force exerted on the load or object to be moved 3 Contraction does not always shorten a muscle: Isometric contraction: no shortening; muscle tension increases but does not exceed the load

Isotonic contraction: muscle shortens because muscle tension exceeds the load Force and duration of contraction vary in response to stimuli of different frequencies and intensities

Motor Unit: The Nerve-Muscle Functional Unit Motor unit = a motor neuron and all (four to several hundred) muscle fibers it supplies

Small motor units in muscles that control fine movements (fingers, eyes) Large motor units in large weight-bearing muscles (thighs, hips)

Muscle fibers from a motor unit are spread throughout the muscle so that a single motor unit causes weak contraction of entire muscle Motor units in a muscle usually contract asynchronously; helps prevent fatigue Muscle Twitch Response of a muscle to a single, brief threshold stimulus

Simplest contraction observable in the lab (recorded as a myogram) Three phases of a twitch: Latent period: events of excitation-contraction coupling Period of contraction: cross bridge formation; tension increases Period of relaxation: Ca2+ reentry into the SR; tension declines to zero

Muscle Twitch Comparisons Different strength and duration of twitches are due to variations in metabolic properties and enzymes between muscles Graded Muscle Responses Variations in the degree of muscle contraction

Required for proper control of skeletal movement Responses are graded by: 1 Changing the frequency of stimulation 2 Changing the strength of the stimulus Response to Change in Stimulus Frequency A single stimulus results in a single contractile responsea muscle twitch

Increase frequency of stimulus (muscle does not have time to completely relax between stimuli) Ca2+ release stimulates further contraction temporal (wave) summation

Further increase in stimulus frequency unfused (incomplete) tetanus If stimuli are given quickly enough, fused (complete) tetany results

Response to Change in Stimulus Strength Threshold stimulus: stimulus strength at which the first observable muscle contraction occurs

Muscle contracts more vigorously as stimulus strength is increased above threshold

Contraction force is precisely controlled by recruitment (multiple motor unit summation), which brings more and more muscle fibers into action Size principle: motor units with larger and larger fibers are recruited as stimulus intensity increases Muscle Tone Constant, slightly contracted state of all muscles

Due to spinal reflexes that activate groups of motor units alternately in response to input from stretch receptors in muscles Keeps muscles firm, healthy, and ready to respond Isotonic Contractions Muscle changes in length and moves the load

Isotonic contractions are either concentric or eccentric: Concentric contractionsthe muscle shortens and does work Eccentric contractionsthe muscle contracts as it lengthens

Isometric Contractions The load is greater than the tension the muscle is able to develop

Tension increases to the muscles capacity, but the muscle neither shortens nor lengthens

Muscle Metabolism: Energy for Contraction ATP is the only source used directly for contractile activities

Available stores of ATP are depleted in 46 seconds ATP is regenerated by: Direct phosphorylation of ADP by creatine phosphate (CP) Anaerobic pathway (glycolysis) Aerobic respiration

Anaerobic Pathway At 70% of maximum contractile activity:

Bulging muscles compress blood vessels Oxygen delivery is impaired Pyruvic acid is converted into lactic acid Lactic acid: Diffuses into the bloodstream Used as fuel by the liver, kidneys, and heart Converted back into pyruvic acid by the liver

Aerobic Pathway Produces 95% of ATP during rest and light to moderate exercise

Fuels: stored glycogen, then bloodborne glucose, pyruvic acid from glycolysis, and free fatty acids

Muscle Fatigue Physiological inability to contract

Occurs when: Ionic imbalances (K+, Ca2+, Pi) interfere with E-C coupling Prolonged exercise damages the SR and interferes with Ca2+ regulation and release

Total lack of ATP occurs rarely, during states of continuous contraction, and causes contractures (continuous contractions) Oxygen Deficit Extra O2 needed after exercise for: Replenishment of

Oxygen reserves Glycogen stores ATP and CP reserves Conversion of lactic acid to pyruvic acid, glucose, and glycogen

Heat Production During Muscle Activity ~ 40% of the energy released in muscle activity is useful as work

Remaining energy (60%) given off as heat Dangerous heat levels are prevented by radiation of heat from the skin and sweating

Force of Muscle Contraction The force of contraction is affected by:

Number of muscle fibers stimulated (recruitment) Relative size of the fibershypertrophy of cells increases strength The force of contraction is affected by:

Frequency of stimulation frequency allows time for more effective transfer of tension to noncontractile components Length-tension relationshipmuscles contract most strongly when muscle fibers are 80120% of their normal resting length Velocity and Duration of Contraction Influenced by: 1 Muscle fiber type 2 Load 3 Recruitment Muscle Fiber Type Classified according to two characteristics: 1 Speed of contraction: slow or fast, according to: Speed at which myosin ATPases split ATP

Pattern of electrical activity of the motor neurons Metabolic pathways for ATP synthesis: Oxidative fibersuse aerobic pathways

Glycolytic fibersuse anaerobic glycolysis Three types: Slow oxidative fibers Fast oxidative fibers Fast glycolytic fibers

Influence of Load load latent period, contraction, and duration of contraction Influence of Recruitment Recruitment faster contraction and duration of contraction Effects of Exercise Aerobic (endurance) exercise: Leads to increased: Muscle capillaries Number of mitochondria Myoglobin synthesis Results in greater endurance, strength, and resistance to fatigue May convert fast glycolytic fibers into fast oxidative fibers

Effects of Resistance Exercise Resistance exercise (typically anaerobic) results in:

Muscle hypertrophy (due to increase in fiber size) Increased mitochondria, myofilaments, glycogen stores, and connective tissue

The Overload Principle Forcing a muscle to work hard promotes increased muscle strength and endurance

Muscles adapt to increased demands Muscles must be overloaded to produce further gains

Smooth Muscle Found in walls of most hollow organs (except heart) Usually in two layers (longitudinal and circular) Peristalsis Alternating contractions and relaxations of smooth muscle layers that mix and squeeze substances through the lumen of hollow organs Longitudinal layer contracts; organ dilates and shortens

Circular layer contracts; organ constricts and elongates

Microscopic Structure Spindle-shaped fibers: thin and short compared with skeletal muscle fibers

Connective tissue: endomysium only SR: less developed than in skeletal muscle Pouchlike infoldings (caveolae) of sarcolemma sequester Ca2+ No sarcomeres, myofibrils, or T tubules

Innervation of Smooth Muscle Autonomic nerve fibers innervate smooth muscle at diffuse junctions

Varicosities (bulbous swellings) of nerve fibers store and release neurotransmitters

Myofilaments in Smooth Muscle Ratio of thick to thin filaments (1:13) is much lower than in skeletal muscle (1:2)

Thick filaments have heads along their entire length No troponin complex; protein calmodulin binds Ca2+

Myofilaments in Smooth Muscle Myofilaments are spirally arranged, causing smooth muscle to contract in a corkscrew manner

Dense bodies: proteins that anchor noncontractile intermediate filaments to sarcolemma at regular intervals Contraction of Smooth Muscle Slow, synchronized contractions

muscle

Cells are electrically coupled by gap junctions Some cells are self-excitatory (depolarize without external stimuli); act as pacemakers for sheets of Rate and intensity of contraction may be modified by neural and chemical stimuli

Contraction of Smooth Muscle Sliding filament mechanism

Final trigger is intracellular Ca2+ Ca2+ is obtained from the SR and extracellular space

Role of Calcium Ions Ca2+ binds to and activates calmodulin

Activated calmodulin activates myosin (light chain) kinase Activated kinase phosphorylates and activates myosin Cross bridges interact with actin

Contraction of Smooth Muscle Very energy efficient (slow ATPases)

Myofilaments may maintain a latch state for prolonged contractions Relaxation requires:

Ca2+ detachment from calmodulin Active transport of Ca2+ into SR and ECF Dephosphorylation of myosin to reduce myosin ATPase activity

Regulation of Contraction Neural regulation: Neurotransmitter binding [Ca2+] in sarcoplasm; either graded (local) potential or action potential

Response depends on neurotransmitter released and type of receptor molecules

Regulation of Contraction Hormones and local chemicals: May bind to G proteinlinked receptors

May either enhance or inhibit Ca2+ entry

Special Features of Smooth Muscle Contraction Stress-relaxation response: Responds to stretch only briefly, then adapts to new length

Retains ability to contract on demand

Enables organs such as the stomach and bladder to temporarily store contents Length and tension changes: Can contract when between half and twice its resting length Special Features of Smooth Muscle Contraction Hyperplasia: Smooth muscle cells can divide and increase their numbers

Example: estrogen effects on uterus at puberty and during pregnancy

Types of Smooth Muscle Single-unit (visceral) smooth muscle: Sheets contract rhythmically as a unit (gap junctions)

Often exhibit spontaneous action potentials Arranged in opposing sheets and exhibit stress-relaxation response

Types of Smooth Muscle: Multiunit Multiunit smooth muscle: Located in large airways, large arteries, arrector pili muscles, and iris of eye

Gap junctions are rare Arranged in motor units Graded contractions occur in response to neural stimuli

Developmental Aspects All muscle tissues develop from embryonic myoblasts

Multinucleated skeletal muscle cells form by fusion Growth factor agrin stimulates clustering of ACh receptors at neuromuscular junctions

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Cardiac and smooth muscle myoblasts develop gap junctions

Developmental Aspects Cardiac and skeletal muscle become amitotic, but can lengthen and thicken

Myoblast-like skeletal muscle satellite cells have limited regenerative ability Injured heart muscle is mostly replaced by connective tissue Smooth muscle regenerates throughout life

Developmental Aspects Muscular development reflects neuromuscular coordination

Development occurs head to toe, and proximal to distal Peak natural neural control occurs by midadolescence Athletics and training can improve neuromuscular control

Developmental Aspects Female skeletal muscle makes up 36% of body mass

Male skeletal muscle makes up 42% of body mass, primarily due to testosterone Body strength per unit muscle mass is the same in both sexes

Developmental Aspects With age, connective tissue increases and muscle fibers decrease

By age 30, loss of muscle mass (sarcopenia) begins Regular exercise reverses sarcopenia

Atherosclerosis may block distal arteries, leading to intermittent claudication and severe pain in leg muscles Muscular Dystrophy Group of inherited muscle-destroying diseases

Muscles enlarge due to fat and connective tissue deposits Muscle fibers atrophy

Muscular Dystrophy Duchenne muscular dystrophy (DMD): Most common and severe type Inherited, sex-linked, carried by females and expressed in males (1/3500) as lack of dystrophin Victims become clumsy and fall frequently; usually die of respiratory failure in their 20s No cure, but viral gene therapy or infusion of stem cells with correct dystrophin genes show promise

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