Download Skeletal Muscle

Muscle Physiology
Chapter 11
• Characteristics
of Muscle Tissue
• Types of Muscle
• Skeletal Muscle
• Motor Units
• Skeletal
Muscle Contraction
• Skeletal Muscle
Metabolism
• Cardiac Muscle
• Smooth Muscle
Characteristics of Muscle
• Responsive (excitable)
– capable of response to chemical signals, electrical
signals, and stretch
• Conductive
– local electrical change in a cell triggers a wave of
excitation that travels along the cell
• Contractile
– cells shorten when stimulated by converting the
chemical energy of ATP into mechanical energy
• Extensible
– cells are capable of being stretched
• Elastic
– cells return to original resting length after being
stretched
• General Characteristics: muscle tissue is composed of
connective tissue, blood vessels, nerves, lymphatics and
muscle cells.
Types of Muscle
• Striated Muscle (cytoplasm has cross striations)
– Striated Skeletal Muscle (voluntary muscle)
– Striated Cardiac Muscle
• Smooth Muscle (cytoplasm without cross striations)
Skeletal Muscle
• Skeletal Muscle is voluntary striated muscle
attached to bones
• Voluntary means under conscious control
• Cells of skeletal muscle tissue are called muscle
fibers = muscle cells = myofibers
• Skeletal muscle cells are as long as the whole
muscle
• Skeletal muscle is a striated muscle.
– striated muscle exhibits microscopic alternating
light and dark transverse bands or cross striations
in the cytoplasm that are from the highly
organized contractile proteins of the cytoskeleton
Muscle – one of
the 600 named units of
the human muscular
system
Fascicle –
bundles of muscle
fibers that form the
visible grain of a
muscle
Muscle Fiber –
individual skeletal
muscle cells
Myofibril – long,
thin cords of contractile
proteins
Myofibrils
Multinucleated Skeletal Muscle Fibers
Sarcolemma
Syncytial Skeletal Muscle Development
Each muscle fiber has multiple
nuclei flattened against the
inside of the sarcolemma.
Multiple nuclei are from the fusion
of multiple myoblasts (derived
from a condensation of
mesenchymal cells) during
development forming a
syncytium.
A syncytium is a multinucleated
mass of cytoplasm surrounded
by a single plasma membrane.
Satellite Cells outside of the
sarcolemma between muscle
fibers can multiply to produce a
small number of new myofibers
or they can add their nuclei to
existing muscle fibers.
Skeletal Muscle Fibers
• Sarcolemma is the specialized plasma membrane of
muscle cells.
– sarcolemma is polarized at rest and can be depolarized by
acetylcholine released by motor neurons
– tubular infoldings of the plasma membrane are called
transverse tubules (T-tubules) that penetrate into the cell
and carry the electrochemical current into the cell
• Sarcoplasm is the specialized cytoplasm of muscle
cells.
– sarcoplasm is filled with highly organized myofibrils (bundles
of parallel protein microfilaments of actin and myosin) and
glycogen for stored energy and myoglobin for storing oxygen
• Sarcoplasmic Reticulum is the specialized
endoplasmic reticulum of muscle cells.
– the sarcoplasmic reticulum is a series of interconnected
tubules connected to dilated, storage sacs called terminal
cisternae that store calcium ions (Ca++)
Sarcomeres: functional units
Muscle Filaments of the Sarcomere
• Sarcomeres are
the functional
units of muscle
• Sarcomeres
extend from one
Z line to the next
Z line.
• Thin filaments
are actin
• Thick filaments
are myosin
• Elastic filaments
are titin
• Ahm, I Zee!
M
• A band extends from myosin tip to myosin
tip.
– A stands for anisotropic which is a term
for the way polarized light passes through
the thick filaments giving it a dark
appearance.
• H band is the central region of the A band
and is a region of myosin without actin.
– H stands for Helle (German for bright).
• M line is a disk of protein that anchors the
myosin filaments.
– M stands for Mittel (German for middle)
• I band is the thin filament region
– I stands for Isotropic: polarized light
passes easily through it giving it a light
appearance
• Z line is a disc of alpha actinin protein that
anchors titin and actin filaments
– Z stands for Zwischen (German for
between)
Regions of
the
Sarcomere
I
Z
A
H
M
I
Z
Regions of the Sarcomere
Electron Micrograph of a Sarcomere
M line
Nucleus
Contractile Proteins and Regulatory Proteins
• Actin and Myosin are contractile proteins
– movements of actin and myosin contract the cell
• Troponin and Tropomyosin are regulatory proteins
that act like a switch that starts and stops
contraction of muscle cells
– The regulatory proteins are dependent upon Ca++
Thick Filaments
• Thick filaments are made of hundreds of
myosin molecules
• Myosin is arranged in bundles with the heads
directed outward in a spiral array around the
bundled tails
Myosin
• Myosin is composed of two entwined
polypeptides (each shaped like a golf club with
a spiral handle)
• The H Zone of a sarcomere is a region
with no heads that contains the M line
Thin Filaments
• Thin filaments are composed of two strands of
fibrous actin composed of 6 or 7 globular actin
(G actin) subunits each with an active site.
• Tropomyosin molecules cover and block the
active sites of 6 or 7 G actin subunits.
• One calcium-binding troponin molecule is
attached to each tropomyosin molecule
Overlap of Thick and Thin Filaments
H band
M line
Elastic Filaments
• Huge springy protein
called Titin is an elastic
filament that connects
the Z disc to the M line
• Titin passes through
the bundles of thick
filaments
• Functions of Titin
– keeps thick and thin
filaments aligned
with each other
– resist overstretching
– help the cell recoil to
its resting length
(provides elasticity)
M
Relaxed versus Contracted Sarcomere
• Muscle cells shorten because
individual sarcomeres shorten by
pulling Z discs closer together.
• Notice that filament overlap
changes, but neither thick nor thick
filaments change length during
shortening.
• During contraction:
– A band length stays the same
– H band shrinks
– I band shrinks
• During relaxation, compressed titin
rebounds and pushes Z disks apart
to the resting length
The Sarcomere in Action
http://www.fbs.leeds.ac.uk/research/contractility/titin.htm
The Sarcomere in Action
http://www.siumed.edu/~dking2/ssb/muscle.htm#1a
Skeletal Muscle Innervation
• Skeletal muscles are
activated by motor
neurons
• Motor Neurons branch out
of the central nervous
system from the skull
(cranial nerves) and the
spine (spinal nerves)
• Somatic motor neurons
innervate skeletal muscles
• Autonomic motor neurons
innervate cardiac muscle,
smooth muscle or glands
Muscle Innervation
Afferent
Efferent
Efferent
Innervation of Skeletal Muscle
• Skeletal muscle cell will not contract
unless it is stimulated by a nerve cell
– nerve cell = neuron
– paralysis is a loss of functional
innervation and results in the loss of
voluntary control of the muscle and
eventually atrophy of the muscle
• Axons of motor neurons are branched.
– each axon can branch a few times
(3-6) or many times (over 200)
– Each axon branch contacts one
muscle fiber
– axons = nerve fibers
• A motor unit is a motor neuron and all
the muscle fibers it innervates
Motor Units
• Muscle cells of a Motor Unit are
dispersed throughout a muscle
– provides ability to sustain longterm contraction as motor units
take turns resting
• Small Motor Units provide Fine
Control
– small motor units contain as few
as 3-6 muscle fibers per nerve
fiber
– example: eye muscles
• Large Motor Units are for Strength
– large motor units have as many
as 1000 muscle fibers per nerve
fiber
– example: gastrocnemius muscle
Neuromuscular Junction
• Neuromuscular Junction (NMJ) is a synapse
between a nerve fiber and a muscle cell.
• Synapse is the functional connection between a
nerve cell and its target cell.
• Components of the NMJ
– terminal boutton (axon terminal, synaptic
knob, terminal button, axonal swelling,
synaptic bulb, end bulb) is the swollen end
of a nerve fiber and contains vesicles of the
neurotransmitter acetylcholine (ACh)
– motor end plate is the specialized region of
muscle cell membrane under the terminal
boutton
– motor end plate membrane has ACh
receptors on junctional folds which bind ACh
released from the nerve
– acetylcholinesterase (AChE) is an enzyme
in the basal lamina in the synaptic cleft that
breaks down ACh and causes relaxation
– synaptic cleft is the gap between the nerve
and muscle cells
– Schwann cells cover the axon and the NMJ
The
Neuromuscular
Junction
Neuromuscular Junction Animation
http://www.mhhe.com/biosci/esp/200
2_general/Esp/folder_structure/su/m4
/s10/sum4s10_7.htm
Muscle and Nerve Electrochemical Communication
• At rest, muscle cell and nerve cell membranes are polarized
(charged). Changes in charge are relayed from one cell to another.
• Membrane polarity or charge is measured in units of volts
– car battery = 12 volts
– flashlight battery = 1.5 volts
– muscle cell membrane = .06 volts or 60 millivolts (mV)
• Difference in charge across the membrane is called the membrane
potential.
– Resting Membrane Potential is established by a Na+/K+
exchange pump that results in high [Na+] outside of cell and high
[K+] and anions inside of cell resulting in a slightly negative
voltage inside the cell (-60 mV).
• Sarcolemma depolarizes in response to motor neuron stimulation
from release of ACh.
• Voltage change spreads across the membrane as an action
potential
Action Potential
Resting membrane
potential of -60 mV is
established by the Na+/K+
ATPase pump and nongated K+ channels (K+ leak
channels)
Opening of Na+ channels is triggered by
ACh and allows Na+ to rush in depolarizing
the membrane.
Membrane depolarization triggers the
opening of voltage activated K+ channels
and closing of Na+ channels. K+ leaves the
cell through the open channels.
The Na+/K+ pump works to restore the
membrane potential back to resting levels.
+75
3
4
2
-90
1
5
1
2
3
4
5
Resting
Membrane
Potential
End Plate
Potential
Action
Potential
Depolarization
Action
Potential
Repolarization
Hyperpolarization
Na+/K+ pump
Na+ out
K+ in
Na+ out
K+ in
Na+ out
K+ in
Na+ out
K+ in
Na+ out
K+ in
non-gated K+ leak
channels
K+ out
K+ out
K+ out
K+ out
K+ out
ACh Receptor
(a ligand-regulated ion
channel)
Closed
Open
letting Na+
in and K+
out
Open as
long as ACh
is present
Open as
long as ACh
is present
Open as
long as ACh
is present
voltage-gated Na+
channel
Closed
Closed
Open and
letting Na+
in
Closed
Closed
voltage-gated K+ channel
Closed
Closed
Slowly
Opening
Open and
letting K+
out
Slowly
Closing
Ion primarily responsible
for the membrane voltage
Na+ pumped
out
K+ leaking
out
Na+ in
K+ out
Na+ in
K+ out
K+ out
Animation:
Establishing a Resting Membrane Potential
http://outreach.mcb.harvard.edu
/animations/actionpotential.swf
Animations:
Sodium-Potassium Exchange
Function of the Neuromuscular Junction
http://highered.mcgrawhill.com/sites/0072437316/student_vie
w0/chapter6/animations.html#
http://highered.mcgrawhill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::
535::/sites/dl/free/0072437316/120107/bio_c.swf
::Function of the Neuromuscular Junction
Muscle Contraction and Relaxation
• Four actions are involved in Muscle
Contraction and Muscle Relaxation:
– Excitation: action potentials in the nerve lead to
formation of action potentials in a muscle fiber
– Excitation-Contraction Coupling: action
potentials on the sarcolemma activate
myofilaments
– Contraction: shortening of a muscle fiber or at
least the formation of tension
– Relaxation: return of a muscle fiber to its resting
length
Excitation
• Nerve signal stimulates voltage-gated calcium channels at the
synaptic knob resulting in exocytosis of synaptic vesicles
containing Ach.
• ACh is released into the synaptic cleft.
Excitation (continued)
• ACh released from the motor neuron binds to ACh receptors
in the sarcolemma.
• Binding of ACh to the receptor causes it to open a channel
for Na+ and K+. A lot of Na+ rushes in and a little K+ rushes
out resulting in a membrane voltage change called the EndPlate Potential. The voltage changes from negative to
positive.
Excitation
(continued)
• The End-Plate Potential (voltage change in the motor
end-plate membrane) opens nearby voltage-gated
Na+ and K+ channels in sarcolemma producing a
depolarization that spreads across the sarcolemma.
The spreading depolarization is the Muscle Action
Potential.
Excitation-Contraction Coupling
• Action potential (membrane depolarization) spreads over the
sarcolemma and down into the T tubules.
• T tubule membrane depolarization triggers the opening of
voltage-gated calcium channels in the sarcoplasmic reticulum
allowing release of Ca++ from the sarcoplasmic reticulum into
the sarcoplasm.
Excitation-Contraction Coupling (cont.)
• Calcium ions (Ca++) released by the SR binds to troponin.
• Troponin-tropomyosin complex changes shape and exposes
active sites on actin.
Contraction
• Myosin ATPase in myosin
head hydrolyzes an ATP
molecule.
• Energy from the ATP “cocks” the
myosin head in a high energy
extended position.
• Myosin head binds to an
exposed active site on actin
forming a cross-bridge.
Contraction
(continued)
12. Power Stroke;
sliding of thin
filament over
thick filament
• Power Stroke:
myosin head releases
the ADP and Pi as
it flexes pulling the
thin filament along.
• If ATP is available,
ATP binds to the myosin head
and it releases the thin filament.
• It will attach to a new active site further down the thin
filament if Ca++ is still available and bound to
troponin.
– to prevent slippage, at any given moment, half of
the heads are bound to a thin filament, while the
other half of the heads are re-setting.
Relaxation
• Nerve stimulation ceases and acetylcholinesterase breaks
down ACh.
• ACh no longer bound to receptors so sarcolemma repolarizes.
Acetylcholinesterase degrades ACh into acetate and choline
which are reabsorbed and recycled by the presynaptic cell.
Enzyme breaks down the ACh within 20 miliseconds.
Relaxation
(continued)
• Active transport (using ATP) by integral membrane protein
pumps in the sarcoplasmic reticulum (SR) removes Ca++
from the sarcoplasm and stores it in the SR where it is
bound to the protein calsequestrin.
• ATP is needed for muscle relaxation as well as muscle
contraction.
Relaxation
(continued)
• Loss of Ca++ from the sarcoplasm results in troponintropomyosin complex moving over the actin active sites which
stops formation of cross bridges and prevents muscle tension.
• Muscle fiber returns to its resting length due to elastic rebound
of titin and the series-elastic components or contraction of
antagonistic muscles.
Animation:
Regulation of Sarcomere Shortening
http://www.blackwellpublishing.com/
matthews/myosin.html
http://www.wiley.com/college/pratt/047
1393878/student/animations/actin_my
osin/actin_myosin.swf
go to unit 9
Rigor Mortis
• Stiffening of the body beginning 3 to 4 hours
after death peaks at 12 hours after death then
diminishes over next 48 to 60 hours.
• Deteriorating sarcoplasmic reticulum releases
calcium.
• Calcium activates actin-myosin cross bridging.
• ATP is no longer produced after death and
without any new ATP, the myosin head
remains bound to the actin (does not release).
• Actin and Myosin fibers remain bound until
myofilaments decay.
Neuromuscular Toxins and Paralysis
• Many pesticides and “nerve gas” are chemicals that inhibit
acetylcholinesterase by binding to it and preventing it from
degrading ACh.
– minor startle response can cause death through spastic
paralysis and suffocation
– atropine is an antidote that works by blocking ACh receptors
• Tetanus or lockjaw is a spastic paralysis caused by a toxin of the
soil bacterium Clostridium tetani.
– the toxin blocks glycine, an inhibitor normally produced by the
spinal cord that prevents overstimulation of muscles.
• Botox - Clostridium botulinum is a related soil bacterium that
produces botulinum toxin that blocks ACh release from motor
neurons.
• Curare causes flaccid paralysis with limp muscles that are unable
to contract.
– Curare is a South American plant toxin used by indigenous
people to make poison darts.
– Curare binds to ACh receptors without activating them.
– Used as a muscle relaxant for surgery, but can cause
respiratory arrest.
Neuromuscular Toxins and Paralysis
• Black Widow Spider Venom causes massive
release of ACh that leads to uncontrolled
muscle spasms.
• Tetrodotoxin (TTX) blocks voltage-gated Na+
channels.
– TTX blocks sodium movement into the neuron
and the action potential along the nerve
membrane ceases.
– A single milligram or less of TTX - an amount that
can be placed on the head of a pin, is enough to
kill an adult.
– 10-100 times more toxic than black widow spider
venom
Myasthenia Gravis
• Autoimmune disease where antibodies bind to ACh
receptors
– Skeletal muscle cells become progressively less
sensitive to ACh
– Symptoms include:
• drooping eyelids and double vision
• difficulty swallowing
• weakness of the limbs
• respiratory failure
• Disease affects mostly women between ages of 20 and 40
• Treated with acteylcholinesterase inhibitors, thymus
removal or immunosuppressive agents
Myasthenia Gravis Symptoms
Drooping eyelids and weakness of muscles of eye movement
Length-Tension Relationship
• Amount of tension generated by a
muscle depends on the length of the
muscle before it is stimulated.
• Overly contracted muscle cells develop
a weak contraction because the thick
filaments are already close to the Z
discs and further contraction results in
the ends of the thick filaments butting
up against the Z disc.
• Overly stretched muscle cells also
develop a weak contraction because
there is too little overlap of thin and
thick filaments which does not allow for
very many cross bridges too form.
• Optimum resting length produces
greatest force when muscle contracts.
Length-Tension Relationship
Muscle Twitch
• Threshold is the minimum voltage necessary
to produce an action potential in a muscle
cell.
– a single brief stimulus at threshold voltage
produces a quick cycle of contraction and
relaxation called a twitch that lasts less than 1/10
second.
• A single twitch contraction is not strong
enough to do any useful work.
Stimulus Frequency and Muscle Tension
Twitch
Treppe
• Twitch: at low frequency (up to 10 stimuli/sec) each
stimulus produces an identical twitch with complete
relaxation in between.
• Treppe: at moderate frequency (between 10-20 stimuli/sec)
the muscle relaxes completely between twitches, but the
tension increases with each twitch because calcium is not
completely reabsorbed into the SR. Also, the heat produced
by muscle contraction increases myosin ATPase efficiency
(as in warm-up exercises).
Stimulus Frequency and Muscle Tension
Incomplete Tetanus
Complete Tetanus
• Incomplete Tetanus results from higher frequency stimulation (20-40
stimuli/second) and gradually generates stronger, sustained contractions.
– each stimulus arrives before the previous one recovers
– this is called temporal summation because it results from the timing of
the stimuli.
• Complete Tetanus usually results from an artificially high stimulation
frequency (40-50 stimuli/second)
– muscle has no time to relax between stimulations
– twitches fuse into a smooth, prolonged contraction
– rarely occurs in the body under natural conditions
Asynchronous Contraction
• The reason for the smoothness of muscle
contraction during muscle tetany is that the motor
units function asynchronously.
– throughout an actively contracting muscle, some
motor units are contracting as others relax.
– the muscle does not lose tension as motor units
take turns developing tension within the muscle.
Energy for Muscle Contraction: ATP
• ATP is the ONLY source of energy for muscle contraction.
• ATP is produced by:
– aerobic respiration
• produces about 36 ATP per glucose molecule
• requires continuous oxygen supply, produces H2O
and CO2 as waste
– anaerobic fermentation
• produces only 2 ATP per glucose molecule
• occurs without oxygen and produces irritating lactic
acid as waste
Phosphagen Enzyme System
Myokinase and
Creatine Kinase
generate ATP in the
absence of O2.
Myokinase uses Pi
from ADP.
Creatine Kinase
uses Pi from
creatine
phosphate.
Sources of ATP During Intense Exercise
• Immediate Energy: About a 10 Second supply of ATP from:
– Aerobic metabolism using O2 released from myoglobin in muscle
cells.
– Phosphagen System of enzymes that transfers Pi to ADP.
• Short-Term Energy: About a 30-40 second supply of ATP from:
– Glycogen-Lactic Acid System uses stored glycogen and anaerobic
metabolism producing lactic acid.
• Long-Term Energy: After about 40 seconds if the respiratory and
cardiovascular systems are functioning well, they can catch up to O2
demand for aerobic respiration and supply more than 90% of ATP
during sustained exercise.
Oxygen Debt
• The need to breath heavily after strenuous
exercise is to provide maximal oxygen for:
– replacing oxygen reserves in myoglobin (red
respiratory pigment in muscle) and hemoglobin
(red respiratory pigment in red blood cells)
– replenishing the phosphagen system
– converting lactic acid back into glucose in kidneys
and liver
– serving the elevated metabolic rate that occurs as
long as the body temperature remains elevated
from exercise
Slow Twitch and Fast Twitch Fibers
• Muscles contain a mixture of muscle fiber types based upon their
metabolism and morphology
• Skeletal Muscle Fiber Types:
1) Slow-twitch fibers (oxidative or red fibers)
– abundnat mitochondria, myoglobin and capillaries
– use aerobic respiration and are resistant to fatigue
– examples: leg and thigh muscles (100msec/twitch)
2) Fast-twitch fibers (glycolytic or white fibers)
– sarcoplasmic reticulum releases calcium quickly so contractions are
quicker
– uses available ATP quickly, then uses enzymes for phosphagen and
glycogen-lactic acid systems, but can fatigue quickly
– examples extraocular eye muscles (7.5 msec/twitch)
3) Intermediate fibers have combined characteristics of fast and slow
twitch and are relatively rare in humans except for endurancetrained athletes.
• Proportions of different muscle types in an individual appear to be
determined genetically: “a born sprinter” or “ a born marathoner” but
small changes in proportions can result from training.
Muscle Fiber Histology
FG = Fast Glycolytic white fibers
SO = Slow Oxidative red fibers
Cardiac Muscle
• Cardiac muscle cells are short, branched, cells that
usually have only one nucleus.
• Cardiac muscle cells are linked to each other by
intercalated discs.
– gap junctions synchronize muscle contractions
– desmosomes keep the cells from pulling apart
• Cardiac muscle cells are Autorhythmic
– initiate their own contraction cycles triggered by
pacemaker cells
• Cardiac muscle cells use aerobic respiration almost
exclusively
–
–
–
–
very vulnerable to interruptions in oxygen supply
use fatty acids for primary energy storage
large, abundant mitochondria resist fatigue
damaged cells are repaired by fibrosis, not mitosis
Cardiac Muscle
Smooth Muscle
• Fusiform cells with one nucleus
– no visible striations or sarcomeres
– thin filaments attach to dense bodies scattered throughout
sarcoplasm and attached to the sarcolemma
– thick filaments are suspended between the thin filaments
– gap junctions spread depolarization from cell to cell
– calcium for contractions comes from poorly developed SR and
from extracellular fluid
• If present, nerve supply is autonomic
– Neurotransmitter can be either ACh or norepinephrine
– Neurotransmitters have different effects in different locations
• Contraction and relaxation is very slow in comparison to striated
muscle.
• Smooth Muscle is very efficient and uses 300 times less ATP to
maintain a given tension than skeletal muscle
• Smooth muscle can be stimulated by neurotransmitters,
hormones, high CO2, low O2, low pH, stretch.
Responses of Smooth Muscle to Stretch
• Stretch opens mechanically-gated calcium channels
causing muscle contraction.
– example: food in the intestines brings on peristalsis
• Stress-relaxation response necessary for hollow organs
that gradually fill (urinary bladder).
– when stretched gently, tissue briefly contracts then
relaxes
• Contracts forcefully when greatly stretched.
• Contraction force matches degree of stretch.
Contraction of Smooth Muscle Cells
These cultured rat aorta smooth muscle cell were immunofluorescently
labeled with primary anti-vinculin mouse monoclonal antibodies followed
by goat anti-mouse Fab fragments conjugated to Cy3 (red fluorescence
emission). Note the prominent staining of the cellular attachment network
in the central portion and periphery of these cells. In addition, the
specimen was simultaneously stained for DNA with the ultravioletabsorbing probe DAPI, and for the cytoskeletal filamentous actin network
with Alexa Fluor 488 conjugated to phalloidin. Images were recorded in
grayscale with a QImaging Retiga Fast-EXi camera system coupled to an
Olympus BX-51 microscope equipped with bandpass emission
fluorescence filter optical blocks provided by Omega Optical. During the
processing stage, individual image channels were pseudocolored with
RGB values corresponding to each of the fluorophore emission spectral
profiles.