Chapter 11

Chapter 11
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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
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
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
Skeletal Muscle
• Voluntary striated muscle attached to
• Muscle fibers (myofibers) as long as 30
• Exhibits alternating light and dark
transverse bands or striations
– reflects overlapping arrangement of
internal contractile proteins
• Under conscious
control (voluntary)
Connective Tissue Elements
• Attachments between muscle and bone
– endomysium, perimysium, epimysium, fascia,
• 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 muscle11-6
The Muscle Fiber
Muscle Fibers
• Multiple flattened nuclei inside cell
– fusion of multiple myoblasts during
– 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
– carry electric current to cell interior
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
– triad = T tubule and 2 terminal cisternea
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
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
Elastic Filaments
• Springy proteins called titin
• Anchor each thick filament to Z disc
• Prevents overstretching of sarcomere
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
Overlap of Thick and Thin Filaments
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
– from one Z disc (Z line) to the next is a sarcomere
Striations and Sarcomeres
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
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
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
Neuromuscular Junctions (Synapse)
• Functional connection between
nerve fiber and muscle cell
• Neurotransmitter (acetylcholine/ACh) released
nerve fiber stimulates muscle cell
• Components of synapse (NMJ)
– synaptic knob is swollen end of nerve fiber (contains
– 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
– Basal lamina = thin layer of collagen and glycoprotein
over all of muscle fiber
The Neuromuscular Junction
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
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
Muscle Contraction and
• 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
– contraction = shortening of muscle fiber
– relaxation = return to resting length
• Images will be used to demonstrate the
steps of each of these actions
Excitation of a Muscle Fiber
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.
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).
Excitation (step 5)
Voltage change in end-plate region (EPP) opens nearby
voltage-gated channels producing an action potential 11-28
Excitation-Contraction Coupling
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
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
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
Contraction (steps 12 and 13)
• Power stroke =
myosin head releases
ADP 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)
Relaxation (steps 14 and 15)
Nerve stimulation ceases and acetylcholinesterase
removes ACh from receptors. Stimulation of the
muscle cell ceases.
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
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
Rigor Mortis
• Stiffening of the body beginning 3 to 4 hours
after death
• Deteriorating sarcoplasmic reticulum releases
• 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
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
Length-Tension Curve
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
• A single twitch contraction is
not strong enough to do any
useful work
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
– contraction phase
• external tension develops as muscle
– relaxation phase
• loss of tension and return
to resting length as calcium returns to SR
Contraction Strength of Twitches
• Threshold stimuli produces twitches
• Twitches unchanged despite increased
• “Muscle fiber obeys an all-or-none law”
contracting to its maximum or not at all
– not a true statement since twitches vary in
• depending upon, Ca2+ concentration, previous stretch
of the muscle, temperature, pH and hydration
• Closer stimuli produce stronger twitches
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
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
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
Isometric and Isotonic
• 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
Muscle Contraction Phases
• Isometric and isotonic phases of lifting
– tension builds though the box is not moving
– muscle begins to shorten
– tension maintained
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
Immediate Energy Needs
• Short, intense exercise (100
m dash)
– oxygen need is supplied by
• 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
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
– muscles obtain glucose from blood and
stored glycogen
Long-Term Energy Needs
• Aerobic respiration needed for prolonged
– 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
• Progressive weakness from use
– ATP synthesis declines as glycogen is
– 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
• 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
» side effects include “heaviness” feeling
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
– replenishing the phosphagen system
– reconverting lactic acid to glucose in kidneys and
– serving the elevated metabolic rate that occurs as
long as the body temperature remains elevated by
Slow- and Fast-Twitch Fibers
• Slow oxidative, slow-twitch fibers
– more mitochondria, myoglobin and
– adapted for aerobic respiration and
resistant to fatigue
– soleus and postural muscles of the
back (100msec/twitch)
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
– extraocular eye muscles, gastrocnemius
and biceps brachii
• Proportions genetically determined
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
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
– mechanical junctions keep the cells from pulling
• Sarcoplasmic reticulum less developed but
large T tubules admit Ca+2 from extracellular
• Damaged cells repaired by fibrosis, not mitosis
Cardiac Muscle 2
• Autorhythmic due to pacemaker cells
• Uses aerobic respiration almost
– large mitochondria make it resistant to
– very vulnerable to interruptions in oxygen
Smooth Muscle
• Fusiform cells with one nucleus
– 30 to 200 microns long and 5 to 10 microns
– no striations, sarcomeres or Z discs
– thin filaments attach to dense bodies
scattered throughout sarcoplasm and on
– SR is scanty and has no T tubules
• calcium for contraction comes from extracellular
• If present, nerve supply is autonomic
– releases either ACh or norepinephrine
Types of Smooth Muscle
• Multiunit smooth muscle
– largest arteries, iris, pulmonary air
passages, arrector pili muscles
– terminal nerve branches synapse on
– independent contraction
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
Stimulation of Smooth Muscle
Stimulation of Smooth Muscle
• Involuntary and contracts without nerve
– 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
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
• power stroke occurs when ATP hydrolyzed
• Thin filaments pull on intermediate filaments
attached to dense bodies on the plasma
– shortens the entire cell in a twisting fashion
Features of Contraction and Relaxation
• Contraction and relaxation very slow in
– 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)
Contraction of Smooth Muscle
Responses to Stretch 1
• Stretch opens mechanically-gated calcium
channels causing muscle response
– food entering the esophagus brings on
• Stress-relaxation response necessary for
hollow organs that gradually fill (urinary
– when stretched, tissue briefly contracts then
Responses to Stretch 2
• Must contract forcefully when greatly
– thick filaments have heads along their
entire length
– no orderly filament arrangement -- no Z
• Plasticity is ability to adjust tension to
degree of stretch such as empty
bladder is not flabby
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
– leads to torn cell membranes and necrosis
• Fascioscapulohumeral MD -- facial and
shoulder muscle only
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
• Disease of women between 20 and 40
• Treated with cholinesterase inhibitors,
thymus removal or immunosuppressive
Myasthenia Gravis
Drooping eyelids and weakness of muscles of eye movement