Download Muscle PowerPoint B

Muscular System
Part B
Muscular mechanics
• The minimal or smallest amount of
stimulation that causes the muscle to
contract is called the threshold stimulus.
• When a muscle cell receives a threshold
stimulus, it contracts to its full extent – an
all-or-none response.
• Give a series of identical stimuli - series of
twitch contractions with complete
relaxation in between contractions
• Strength of contractions increases slightly
each time – staircase effect or treppe
Time
• Latent period – Ca++ is released, filament
movement takes up slack – 2 milliseconds
• Contraction period – 10 – 100 milliseconds
• Relaxation period - 10 – 100 milliseconds
• Refractory period – time after a contraction
until the muscle is able to respond to a second
stimulus.
– Skeletal muscle – 5 msec
– Cardiac muscle – 300 msec (0.3 sec)
• When stimuli do not allow muscle to relax
completely between contractions, the
muscle contraction becomes sustained.
• If stimulation is great enough, get a
sustained contraction called a tetanic
contraction or tetanus.
Sustained contraction
Tetanic contraction
Muscle fiber length
Whole muscle myogram
• A brief, single stimulus results in a twitch
contraction.
• A twitch is a brief contraction of all the
muscle fibers in a motor unit.
• When a motor neuron fires, all of its muscle
fibers contract fully.
• Some motor units are more easily stimulated
than others.
• If only some of the motor units in a muscle
contract, the entire muscle contracts partially.
• The process of adding more motor units for a
greater muscle contraction is called
recruitment or multiple motor unit
summation.
• To prevent fatigue, there is
asynchronous recruitment of motor
units.
• Recruitment varies with the type of muscle
fibers.
• Muscles maintain a firmness at rest called
muscle tone .
Types of muscle contraction
• Isotonic contraction (iso = same, tonus =
tension) results in movement at a joint
– Because shortening of the muscle occurs it is called
a concentric contraction.
– When the muscle lengthens it is called an eccentric
contraction.
• Isometric contraction (iso= same, metric
= measure) the force of contraction
changes, but the muscle length remains
the same.
Cardiac Muscle – similar to
skeletal muscle in:
• Striations – caused by organization of
myofilaments
• Contains troponin and tropomyosin – site of
activation of cross-bridge activity by Ca++
• Clear length-tension relationship
• Numerous mitochondria and myoglobin (for
aerobic respiration)
• T tubules and moderately well developed
sarcoplasmic reticulum (T tubule at Z line)
Cardiac Muscle – differs from
skeletal muscle in:
• Shorter, larger diameter than skeletal
muscle
• Branch, forming 3-D networks
• Usually only one nucleus
• Autorythmicity –influenced by nervous
system and hormones
• Sarcoplasm is more abundant with more
mitochondria
• Only one t-tubule per sarcomere
• Well developed S.R., but less than skeletal
muscle; cisternae store less Ca++.
• During contraction a lot of Ca++ enters cell
from the extracellular fluid in the t-tubule
and extracellular fluid around the cell, so
extracellular calcium partially controls
the strength and length of contraction.
• Intercalated discs – desmosomes; gap
junctions
• Two networks – atria and ventricles – cells
contract together linked by gap junctions functional syncytium
Cardiac muscle physiology
• Contraction starts at the pacemaker or
sinoatrial node.
• Autorhythmicity
• Contraction due in large part to influx of
Ca++ from ECF
• Resting potential of -90 mV
• Opening of voltage-gated Na+ channels
reverses polarity to +30 mV
• Membrane potential rapidly reverses due
to influx of Na+
• Plateau phase lasts several hundred
milliseconds due to slow influx of Ca++
(and slowing of exit of K+)
• Repolarization is due to rapid out flow of
K+ ions.
• Remains contracted 10-15 times longer
• Long refractory period
– Allows for filling of heart chambers
– Prevents tetanic contractions
• In skeletal muscle the amount of Ca2+
released is sufficient to bind all of the
troponin molecules
• In cardiac muscle only a portion of
troponin has bound Ca2+; allows for
changes in contractility
• In cardiac muscle SR does not release
enough Ca2+ to activate muscle
contraction.
• Ca2+ entering cell during plateau phase
triggers release of calcium from SR
(calcium-induced calcium release)
• DHP channels: RyR is 1:1
• Release of “calcium sparks” sum to trigger
release
• Increased cytosolic calcium
Removal of Ca2+ from cytosol
• Ca2+ATPase in SR runs continuously and
is further activated by high cytoplasmic
calcium levels (extracellular Ca++ that
entered cell can be stored for next
contraction)
• Also Ca2+ATPase located in sarcolemma
• Na+/Ca++ exchange proteins (3:1 ;
secondary active transport)
Effects of extracellular K+ on heart
• Changes in K+ in ECF alter the
concentration gradient across sarcolemma
– Leads to ectopic foci and cardiac arrhythmias
– Decrease in action potential leads to weak
contractions and dilation of heart
– At extremes, heart can stop
Effects of extracellular Ca++ on
heart
• Rise in ECF Ca++ increases strength of
contraction by prolonging plateau phase
– Tends to contract spastically
– Drugs can influence Ca++ movement across
sarcolemma (calcium channel blockers, digitalis
e.g.)
Inotropy
• Positive inotropes increase contractility of heart
– Sympathetic nervous system stimulation
– Catecholamine hormones (epinephrine)
– Digitalis
– Increased heart rate
• Negative inotropes decrease contractility
– Decreased heart rate
– Coronary artery disease
– Certain drugs (calcium channel blockers)
Starling’s Law
• Within certain physiological limits, an
increase in the stretching of the ventricles
causes an increase in the force of
contraction of the heart.
• This allows for instantaneous regulation of
contraction for increases in blood entering
heart
Smooth muscle
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Nonstriated and involuntary
Cells smaller than skeletal muscle cells
Spindle-shaped
Single nucleus
NO T tubules
Different arrangement of myofilaments
Thin, thick and intermediate filaments
Smooth muscle
• Thick and thin filaments not arranged in
sarcomeres
• Thick filaments are longer than in skeletal
muscle
• Thin filaments lack troponin
• 10-15 thin filaments/ thick (skeletal 2:1)
• Intermediate fibers act as cytoskeleton
• Typically less SR than in skeletal muscle
• Intermediate filaments attach to dense
bodies ( act like Z discs)
• Intermediate fibers connect dense bodies
• Thick- and thin-filament contractile units
oriented slightly diagonally in a diamondshaped lattice pattern
• Contraction causes the lattice to decrease
in length and expand from side to side.
• During contraction, the sliding thick and
thin filaments generate tension that is
transmitted to the intermediate filaments,
which pull on the dense bodies in the
sarcoplasm and those attached to the
sarcolemma.
• Isolated smooth muscle cells contract by
twisting into a helical shape, but this is
prevented in intact tissues due to their
attachment to other cells.
Gap Junctions
• Often connect smooth muscle cells
• May be temporary, and may be under
hormonal control
• The electrical joining of smooth muscle
cells is the basis for classifying smooth
muscle into two types:
Visceral (single-unit) smooth muscle
• Many cells acting together
Multiunit smooth muscle
• Cells contract in small groups
Single-unit smooth
muscle
Multiunit Smooth
Muscle
Visceral (single-unit) smooth muscle
• More common type
• Wrap-around sheets
• Fibers form networks that contract
together
• Connected by gap junctions
• Some cells also have autorhythmicity
• Largely responsible for peristalsis
Multiunit Smooth Muscle
• Individual fibers within motor units; few
gap junctions
• In walls of large arteries, large airways,
arrector pili, iris muscles and ciliary body
in eye.
• Contracts only after stimulation by motor
neuron or hormones
Physiology of Smooth Muscle
• Contractions start slower and last longer
• Can shorten and extend to greater extent
• Resting potential is much lower and can
vary over time due to automatic cyclical
changes in the rate at which Na+ is
pumped across the membrane.
• “Slow wave”
• Sodium is not the major carrier of current
during an action potential, instead it is
Ca2+ which enters through voltage-gated
channels
• Also have receptor-activated or chemically
activated Ca2+ channels
• Repolarization due to outflow of K+ though
voltage-gated channels and some
channels sensitive to intracellular Ca2+
levels
Physiology of Smooth Muscle
• Calcium ions come from the small amount
of S.R. and from extracellular fluid
through DHP channels
• Instead of troponin, contains calmodulin
which regulates contraction
• Myosin-linked regulation
• Camodulin binds with Ca++ and activates
myosin light chain kinase (MLCK)
• MLCK uses ATP to add a phosphate group to
the myosin head. Myosin can then bind to actin
• ATP for actual contraction is separate
• Enzymes work slowly (100 x slower than
skeletal muscle)
• Calmodulin is sensitive to Ca2+ conc. in ICF
– At 10-7 M Ca2+ , no calcium is bound
– At 10-4 M Ca2+ all 4 calmodulin sites are bound and
rate of phosphorylation is maximal
– In between see gradations in contractile force
Relaxation of Smooth Muscle
• When Ca2+ levels fall, calmodulin is no
longer active and phosphorylation of
myosin is reversed by the enzyme myosin
light-chain phosphotase (MLCP)
• Ca2+ also leaves the cell slowly, which
delays relaxation and provides for smooth
muscle tone.
• Sustained tone is important, and in some
cases smooth muscle can maintain a low
level of active tension for long periods of
time; a long sustained contraction is called
tonus rather than tetanus
Regulation of Smooth Muscle
contraction
• Responds to signals from autonomic nervous
system ( responds to ACh and norepinephrine)
• Some have no nerve supply and depolarize
spontaneously or to ligands that bind to G
protein linked receptors
• Many also contract or relax in response to
stretching, hormones or local factors (such as
changes in pH, oxygen or carbon dioxide
levels, temperature or ion concentration).
• Enhances or inhibits entry of Ca2+
Origin and Insertions
• Origin – the attachment of a muscle to the
less movable part (torso, etc.)
• Insertion – the attachment of a muscle to
the more movable part
Interactions of muscles
• Prime mover – the muscle primarily
responsible for a movement
• Synergist – stabilizes or assists prime
mover
• Antagonist – opposes action of prime
mover and must relax for prime mover to
contract completely
Major muscles will be covered in
lab.
Life Span Changes
• Develops from mesoderm cells called
myoblasts
• Multinucleate skeletal muscle cells form
through fusion of myoblasts to form
myotubes
• Fibers are contracting at 7 weeks
• ACh receptors sprout over surface of
myoblast
• Agrin released by nerve endings
stimulates clustering of ACh receptors
• Remaining receptor sites dispersed
• Electrical activity in the motor neurons
plays a critical role in maturation of muscle
fibers
• The number of fast and slow fiber types is
determined.
• Myoblasts producing cardiac and smooth
muscle fibers do not fuse. Both develop
gap junctions early. Cardiac muscle is
pumping blood 3 weeks after fertilization.
Repair of muscle
• Skeletal and cardiac muscle cells stop
dividing early, but retain ability to lengthen
and thicken in a growing child and to
hypertrophy in adults.
• After first year, growth of skeletal muscle
is by hypertrophy.
• Enlarged fibers may split down middle
• Satellite cells (stem cells)repair injured
fibers and may allow a very limited
regeneration of fibers.
• Most repair by fibrosis
Repair of cardiac muscle
• Cardiac fibers do divide at a modest rate.
• Injured heart muscle repaired mostly by
fibrosis (scar tissue).
• Fibers can hypertrophy and enlarge heart
Repair of Smooth Muscle
• Limited to good capacity for division and
regeneration throughout life
• Some increase due to hyperplasia
• New fibers can arise from pericytes (stem
cells)
• Proliferate in atheroscerolsis
Development
• At birth movements are uncoordinated and
reflexive
• Develops head-to-toe and proximal-todistal
• Through childhood control becomes more
sophisticated.
• Early hand dominance
• Midadolescence reach peak of natural
neural control of muscles
Male vs. Female
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Strength has a biological basis
Women 36% muscle
Men 42% muscle
Primarily due to effects of testosterone
Strength per unit mass is the same in both
sexes
Aging changes
• Connective tissue and fat increase and
there is a slow, continuous reduction in the
number of muscle fibers and loss of
strength.
• At age 30 sarcopenia begins to occur as
proteins degrade faster than they are
replaced. (regulatory molecules?)
• Up to 30% of muscle fibers may be lost by
age of 80.
• Loss of fibers reduces size of motor units
• More motor units must be recruited to
move a given weight, so requires more
effort.
• Fast-twitch glycolytic fibers atrophy earlier
than slow-twitch oxidative fibers.
• Posture not affected until very late in life.
• Reduction of ability of muscle to adapt to
exercise.
• Some loss is disuse atrophy
• Impairment of synthesis of new muscle
proteins
• Reduction in nerve activity due to changes
in nervous system
– Loss of motor neurons
– Reduction in synthesis of ACh
– Contributes to muscle fiber atrophy and
efficiency of stimulation