11-1

Chapter 11

Lecture Outline

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Muscle Tissue

• Types and characteristics of muscular tissue• Microscopic anatomy of skeletal muscle• Nerve-Muscle relationship• Behavior of skeletal muscle fibers• Behavior of whole muscles• Muscle metabolism• Cardiac and smooth muscle

11-3

Introduction to Muscle

• Movement is a fundamental characteristic of all living things

• Cells capable of shortening and converting the chemical energy of ATP into mechanical energy

• Types of muscle– skeletal, cardiac and smooth

• Physiology of skeletal muscle– basis of warm-up, strength, endurance and

fatigue

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Characteristics of Muscle

• Responsiveness (excitability)– to chemical signals, stretch and electrical

changes across the plasma membrane

• Conductivity– local electrical change triggers a wave of

excitation that travels along the muscle fiber

• Contractility -- shortens when stimulated

• Extensibility -- capable of being stretched

• Elasticity -- returns to its original resting length after being stretched

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Skeletal Muscle

• Voluntary striated muscle attached to bones

• Muscle fibers (myofibers) as long as 30 cm

• Exhibits alternating light and dark transverse bands or striations– reflects overlapping arrangement of

internal contractile proteins

• Under conscious control (voluntary)

11-6

Connective Tissue Elements• Attachments between muscle and bone

– endomysium, perimysium, epimysium, fascia, tendon

• Collagen is extensible and elastic– stretches slightly under tension and recoils

when released• protects muscle from injury• returns muscle to its resting length

• Elastic components– parallel components parallel muscle cells– series components joined to ends of muscle

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The Muscle Fiber

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Muscle Fibers

• Multiple flattened nuclei inside cell membrane– fusion of multiple myoblasts during

development– unfused satellite cells nearby can multiply to

produce a small number of new myofibers

• Sarcolemma has tunnel-like infoldings or transverse (T) tubules that penetrate the cell– carry electric current to cell interior

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Muscle Fibers 2

• Sarcoplasm is filled with – myofibrils (bundles of myofilaments)– glycogen for stored energy and myoglobin

for binding oxygen

• Sarcoplasmic reticulum = smooth ER– network around each myofibril– dilated end-sacs (terminal cisternea) store

calcium– triad = T tubule and 2 terminal cisternea

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Thick Filaments

• Made of 200 to 500 myosin molecules– 2 entwined polypeptides (golf clubs)

• Arranged in a bundle with heads directed outward in a spiral array around the bundled tails– central area is a bare zone with no heads

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Thin Filaments• Two intertwined strands fibrous (F) actin

– globular (G) actin with an active site

• Groove holds tropomyosin molecules– each blocking 6 or 7 active sites of G actins

• One small, calcium-binding troponin molecule on each tropomyosin molecule

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Elastic Filaments

• Springy proteins called titin

• Anchor each thick filament to Z disc

• Prevents overstretching of sarcomere

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Regulatory and Contractile Proteins

• Myosin and actin are contractile proteins• Tropomyosin and troponin = regulatory proteins

– switch that starts and stops shortening of muscle cell– contraction activated by release of calcium into sarcoplasm

and its binding to troponin, – troponin moves tropomyosin off the actin active sites

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Overlap of Thick and Thin Filaments

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Striations = Organization of Filaments• Dark A bands (regions) alternating with lighter I bands (regions)

– anisotrophic (A) and isotropic (I) stand for the way these regions affect polarized light

• A band is thick filament region– lighter, central H band area

contains no thin filaments• I band is thin filament region

– bisected by Z disc protein called connectin, anchoring elastic and thin filaments

– from one Z disc (Z line) to the next is a sarcomere

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Striations and Sarcomeres

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Relaxed and Contracted Sarcomeres

• Muscle cells shorten because their individual sarcomeres shorten – pulling Z discs closer together– pulls on sarcolemma

• Notice neither thick nor thin filaments change length during shortening

• Their overlap changes as sarcomeres shorten

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Nerve-Muscle Relationships

• Skeletal muscle must be stimulated by a nerve or it will not contract

• Cell bodies of somatic motor neurons in brainstem or spinal cord

• Axons of somatic motor neurons = somatic motor fibers– terminal branches supply one muscle fiber

• Each motor neuron and all the muscle fibers it innervates = motor unit

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Motor Units• A motor neuron and the muscle

fibers it innervates– dispersed throughout the muscle– when contract together causes weak

contraction over wide area– provides ability to sustain long-term

contraction as motor units take turns resting (postural control)

• Fine control– small motor units contain as few as

20 muscle fibers per nerve fiber– eye muscles

• Strength control– gastrocnemius muscle has 1000

fibers per nerve fiber

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Neuromuscular Junctions (Synapse)

• Functional connection between nerve fiber and muscle cell

• Neurotransmitter (acetylcholine/ACh) released from nerve fiber stimulates muscle cell

• Components of synapse (NMJ)– synaptic knob is swollen end of nerve fiber (contains

ACh)– junctional folds region of sarcolemma

• increases surface area for ACh receptors• contains acetylcholinesterase that breaks down ACh and

causes relaxation– synaptic cleft = tiny gap between nerve and muscle

cells– Basal lamina = thin layer of collagen and glycoprotein

over all of muscle fiber

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The Neuromuscular Junction

11-22

Neuromuscular Toxins

• Pesticides (cholinesterase inhibitors) – bind to acetylcholinesterase and prevent it

from degrading ACh– spastic paralysis and possible suffocation

• Tetanus or lockjaw is spastic paralysis caused by toxin of Clostridium bacteria– blocks glycine release in the spinal cord and

causes overstimulation of the muscles

• Flaccid paralysis (limp muscles) due to curare that competes with ACh– respiratory arrest

11-23

Electrically Excitable Cells

• Plasma membrane is polarized or charged – resting membrane potential due to Na+ outside

of cell and K+ and other anions inside of cell– difference in charge across the membrane =

resting membrane potential (-90 mV cell)

• Stimulation opens ion gates in membrane– ion gates open (Na+ rushes into cell and K+

rushes out of cell)• quick up-and-down voltage shift = action potential

– spreads over cell surface as nerve signal

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Muscle Contraction and Relaxation

• Four actions involved in this process– excitation = nerve action potentials lead to

action potentials in muscle fiber– excitation-contraction coupling = action

potentials on the sarcolemma activate myofilaments

– contraction = shortening of muscle fiber – relaxation = return to resting length

• Images will be used to demonstrate the steps of each of these actions

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Excitation of a Muscle Fiber

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Excitation (steps 1 and 2)

• Nerve signal opens voltage-gated calcium channels. Calcium stimulates exocytosis of synaptic vesicles containing ACh = ACh release into synaptic cleft.

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Excitation (steps 3 and 4)

Binding of ACh to receptor proteins opens Na+ and K+ channels resulting in jump in RMP from -90mV to +75mV forming an end-plate potential (EPP).

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Excitation (step 5)

Voltage change in end-plate region (EPP) opens nearby voltage-gated channels producing an action potential

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Excitation-Contraction Coupling

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Excitation-Contraction Coupling (steps 6 and 7)

Action potential spreading over sarcolemma enters T tubules -- voltage-gated channels open in T tubules causing calcium gates to open in SR

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Excitation-Contraction Coupling (steps 8 and 9)

• Calcium released by SR binds to troponin• Troponin-tropomyosin complex changes shape

and exposes active sites on actin

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Contraction (steps 10 and 11)

• Myosin ATPase in myosin head hydrolyzes an ATP molecule, activating the head and “cocking” it in an extended position

• It binds to actin active site forming a cross-bridge

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Contraction (steps 12 and 13)• Power stroke =

myosin head releasesADP and phosphate as it flexes pulling the thin filament past the thick

• With the binding of more ATP, the myosin head extends to attach to a new active site– half of the heads are bound to a thin

filament at one time preventing slippage– thin and thick filaments do not become

shorter, just slide past each other (sliding filament theory)

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Relaxation (steps 14 and 15)

Nerve stimulation ceases and acetylcholinesterase removes ACh from receptors. Stimulation of the muscle cell ceases.

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Relaxation (step 16)

• Active transport needed to pump calcium back into SR to bind to calsequestrin

• ATP is needed for muscle relaxation as well as muscle contraction

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Relaxation (steps 17 and 18)

• Loss of calcium from sarcoplasm moves troponin-tropomyosin complex over active sites– stops the production or maintenance of tension

• Muscle fiber returns to its resting length due to recoil of series-elastic components and contraction of antagonistic muscles

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Rigor Mortis

• Stiffening of the body beginning 3 to 4 hours after death

• Deteriorating sarcoplasmic reticulum releases calcium

• Calcium activates myosin-actin cross-bridging and muscle contracts, but can not relax.

• Muscle relaxation requires ATP and ATP production is no longer produced after death

• Fibers remain contracted until myofilaments decay

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Length-Tension Relationship

• Amount of tension generated depends on length of muscle before it was stimulated– length-tension relationship (see graph next slide)

• Overly contracted (weak contraction results)– thick filaments too close to Z discs and can’t slide

• Too stretched (weak contraction results)– little overlap of thin and thick does not allow for very

many cross bridges too form

• Optimum resting length produces greatest force when muscle contracts– central nervous system maintains optimal length

producing muscle tone or partial contraction

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Length-Tension Curve

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Muscle Twitch in Frog

• Threshold = voltage producing an action potential– a single brief stimulus at that

voltage produces a quick cycle of contraction and relaxation called a twitch (lasting less than 1/10 second)

• A single twitch contraction is not strong enough to do any useful work

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Muscle Twitch in Frog 2

• Phases of a twitch contraction– latent period (2 msec delay)

• only internal tension is generated• no visible contraction occurs since

only elastic components are being stretched

– contraction phase• external tension develops as muscle

shortens

– relaxation phase • loss of tension and return

to resting length as calcium returns to SR

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Contraction Strength of Twitches

• Threshold stimuli produces twitches• Twitches unchanged despite increased

voltage• “Muscle fiber obeys an all-or-none law”

contracting to its maximum or not at all– not a true statement since twitches vary in

strength• depending upon, Ca2+ concentration, previous stretch

of the muscle, temperature, pH and hydration

• Closer stimuli produce stronger twitches

11-43

Recruitment and Stimulus Intensity

• Stimulating the whole nerve with higher and higher voltage produces stronger contractions

• More motor units are being recruited– called multiple motor unit summation– lift a glass of milk versus a whole gallon of milk

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Twitch and Treppe Contractions

• Muscle stimulation at variable frequencies– low frequency (up to 10 stimuli/sec)

• each stimulus produces an identical twitch response

– moderate frequency (between 10-20 stimuli/sec)• each twitch has time to recover but develops more

tension than the one before (treppe phenomenon)– calcium was not completely put back into SR

– heat of tissue increases myosin ATPase efficiency

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Incomplete and Complete Tetanus

• Higher frequency stimulation (20-40 stimuli/second) generates gradually more strength of contraction– each stimuli arrives before last one recovers

• temporal summation or wave summation

– incomplete tetanus = sustained fluttering contractions

• Maximum frequency stimulation (40-50 stimuli/second)– muscle has no time to relax at all– twitches fuse into smooth, prolonged contraction called

complete tetanus– rarely occurs in the body

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Isometric and Isotonic Contractions

• Isometric muscle contraction– develops tension without changing length– important in postural muscle function and

antagonistic muscle joint stabilization• Isotonic muscle contraction

– tension while shortening = concentric– tension while lengthening = eccentric

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Muscle Contraction Phases

• Isometric and isotonic phases of lifting – tension builds though the box is not moving– muscle begins to shorten– tension maintained

11-48

ATP Sources

• All muscle contraction depends on ATP• Pathways of ATP synthesis

– anaerobic fermentation (ATP production limited)• without oxygen, produces toxic lactic acid

– aerobic respiration (more ATP produced)• requires continuous oxygen supply, produces H2O and

CO2

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Immediate Energy Needs

• Short, intense exercise (100 m dash)– oxygen need is supplied by

myoglobin

• Phosphagen system– myokinase transfers Pi groups

from one ADP to another forming ATP

– creatine kinase transfers Pi groups from creatine phosphate to make ATP

• Result is power enough for 1 minute brisk walk or 6 seconds of sprinting

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Short-Term Energy Needs

• Glycogen-lactic acid system takes over– produces ATP for 30-40 seconds of

maximum activity• playing basketball or running around baseball

diamonds

– muscles obtain glucose from blood and stored glycogen

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Long-Term Energy Needs

• Aerobic respiration needed for prolonged exercise– Produces 36 ATPs/glucose molecule

• After 40 seconds of exercise, respiratory and cardiovascular systems must deliver enough oxygen for aerobic respiration– oxygen consumption rate increases for first 3-4

minutes and then levels off to a steady state

• Limits are set by depletion of glycogen and blood glucose, loss of fluid and electrolytes

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Fatigue

• Progressive weakness from use– ATP synthesis declines as glycogen is

consumed– sodium-potassium pumps fail to maintain

membrane potential and excitability– lactic acid inhibits enzyme function– accumulation of extracellular K+

hyperpolarizes the cell– motor nerve fibers use up their acetylcholine

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Endurance

• Ability to maintain high-intensity exercise for >5 minutes– determined by maximum oxygen uptake

• VO2 max is proportional to body size, peaks at age 20, is larger in trained athlete and males

– nutrient availability• carbohydrate loading used by some athletes

– packs glycogen into muscle cells– adds water at same time (2.7 g water with each

gram/glycogen)» side effects include “heaviness” feeling

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Oxygen Debt• Heavy breathing after strenuous exercise

– known as excess postexercise oxygen consumption (EPOC)

– typically about 11 liters extra is consumed

• Purposes for extra oxygen– replace oxygen reserves (myoglobin, blood

hemoglobin, in air in the lungs and dissolved in plasma)

– replenishing the phosphagen system– reconverting lactic acid to glucose in kidneys and

liver– serving the elevated metabolic rate that occurs as

long as the body temperature remains elevated by exercise

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Slow- and Fast-Twitch Fibers

• Slow oxidative, slow-twitch fibers– more mitochondria, myoglobin and

capillaries– adapted for aerobic respiration and

resistant to fatigue– soleus and postural muscles of the

back (100msec/twitch)

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Slow and Fast-Twitch Fibers

• Fast glycolytic, fast-twitch fibers– rich in enzymes for phosphagen and

glycogen-lactic acid systems– sarcoplasmic reticulum releases calcium

quickly so contractions are quicker (7.5 msec/twitch)

– extraocular eye muscles, gastrocnemius and biceps brachii

• Proportions genetically determined

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Strength and Conditioning

• Strength of contraction– muscle size and fascicle arrangement

• 3 or 4 kg / cm2 of cross-sectional area

– size of motor units and motor unit recruitment– length of muscle at start of contraction

• Resistance training (weight lifting)– stimulates cell enlargement due to synthesis of

more myofilaments

• Endurance training (aerobic exercise)– produces an increase in mitochondria, glycogen and

density of capillaries

11-58

Cardiac Muscle 1

• Thick cells shaped like a log with uneven, notched ends

• Linked to each other at intercalated discs– electrical gap junctions allow cells to stimulate their

neighbors– mechanical junctions keep the cells from pulling

apart

• Sarcoplasmic reticulum less developed but large T tubules admit Ca+2 from extracellular fluid

• Damaged cells repaired by fibrosis, not mitosis

11-59

Cardiac Muscle 2

• Autorhythmic due to pacemaker cells

• Uses aerobic respiration almost exclusively– large mitochondria make it resistant to

fatigue– very vulnerable to interruptions in oxygen

supply

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Smooth Muscle• Fusiform cells with one nucleus

– 30 to 200 microns long and 5 to 10 microns wide

– no striations, sarcomeres or Z discs– thin filaments attach to dense bodies

scattered throughout sarcoplasm and on sarcolemma

– SR is scanty and has no T tubules• calcium for contraction comes from extracellular

fluid

• If present, nerve supply is autonomic– releases either ACh or norepinephrine

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Types of Smooth Muscle

• Multiunit smooth muscle– largest arteries, iris, pulmonary air

passages, arrector pili muscles– terminal nerve branches synapse on

myocytes– independent contraction

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Types of Smooth Muscle

• Single-unit smooth muscle– most blood vessels and viscera as circular

and longitudinal muscle layers– electrically coupled by gap junctions– large number of cells contract as a unit

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Stimulation of Smooth Muscle

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Stimulation of Smooth Muscle

• Involuntary and contracts without nerve stimulation– hormones, CO2, low pH, stretch, O2 deficiency– pacemaker cells in GI tract are autorhythmic

• Autonomic nerve fibers have beadlike swellings called varicosities containing synaptic vesicles– stimulates multiple myocytes at diffuse

junctions

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Features of Contraction and Relaxation

• Calcium triggering contraction is extracellular– calcium channels triggered to open by voltage,

hormones, neurotransmitters or cell stretching• calcium ions bind to calmodulin• activates light-chain myokinase which activates myosin

ATPase • power stroke occurs when ATP hydrolyzed

• Thin filaments pull on intermediate filaments attached to dense bodies on the plasma membrane– shortens the entire cell in a twisting fashion

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• Contraction and relaxation very slow in comparison– slow myosin ATPase enzyme and slow

pumps that remove Ca+2

• Uses 10-300 times less ATP to maintain the same tension– latch-bridge mechanism maintains tetanus

(muscle tone)• keeps arteries in state of partial contraction

(vasomotor tone)

Features of Contraction and Relaxation

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Contraction of Smooth Muscle

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Responses to Stretch 1

• Stretch opens mechanically-gated calcium channels causing muscle response– food entering the esophagus brings on

peristalsis

• Stress-relaxation response necessary for hollow organs that gradually fill (urinary bladder)– when stretched, tissue briefly contracts then

relaxes

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• Must contract forcefully when greatly stretched– thick filaments have heads along their

entire length– no orderly filament arrangement -- no Z

discs

• Plasticity is ability to adjust tension to degree of stretch such as empty bladder is not flabby

Responses to Stretch 2

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Muscular Dystrophy• Hereditary diseases - skeletal muscles

degenerate and are replaced with adipose

• Disease of males– appears as child begins to walk– rarely live past 20 years of age

• Dystrophin links actin filaments to cell membrane– leads to torn cell membranes and necrosis

• Fascioscapulohumeral MD -- facial and shoulder muscle only

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Myasthenia Gravis• Autoimmune disease - antibodies attack

NMJ and bind ACh receptors in clusters– receptors removed– less and less sensitive to ACh

• drooping eyelids and double vision, difficulty swallowing, weakness of the limbs, respiratory failure

• Disease of women between 20 and 40

• Treated with cholinesterase inhibitors, thymus removal or immunosuppressive agents

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Myasthenia Gravis

Drooping eyelids and weakness of muscles of eye movement