LECTURE 8: MUSCULAR CONTRACTION Flashcards
Classification of muscle (morphological
and functional)
-smooth muscle
-striated muscle
Types of Striated muscle
-skeletal muscle
-cardiac muscle.
comprise muscle fibers, composed of thin and thick filaments
Striated Muscle
Location of Smooth Muscle
Internal Organs
Location of Striated muscle
attached to the skeleton
Most muscles contract when __________ send signals to them, initiating a series of events that cause the muscles to generate force and become ________
-neurons
-shorter
Each and every skeletal
muscle fiber in vertebrates
is innervated by a single
_______________ but a certain
neuron may innervate a
number of fibers.
motor neuron
Three principal kinds of movement:
– ameboid
– ciliary and flagellar
– muscular
The motor neurons are
__________ and only if they
send _______________ to the
muscles that the muscles
are activated.
-excitatory
-synaptic input
consists of a single motor neuron and all the muscle fibers it controls. and is the functional unit of skeletal muscle control
motor unit
contraction of skeletal muscle results from
___________________ travelling down somatic
motor axons originating in the CNS
action potentials
transfer of signal from nerve to muscle occurs
at the ____________________, also called
myoneural junction or motor endplate
neuromuscular junction
A special type of synapse exhibiting close
association between the membranes of a neuron and a muscle fibre
myoneural junction /motor endplate
-The synaptic contact between
a nerve fiber and a muscle
fiber
-Nerve impulses bring about
the release of a
neurotransmitter that cross
the synaptic cleft
-Signals the muscle fiber to
contract
Neuromuscular junction
The stimulus leading to contraction of a muscle
fiber is an action potential in a motor neuron that makes a ________ with the muscle fiber.
synapse
Muscle Contraction = ____________________
The active generation of tension within muscle fiber
- consists of parallel multinucleate
fibers (contains many myofibrils) - attached to bones or other
anchor points through tough
connective tissue bands (tendons)
skeletal muscles
sarcomeres, arranged end-to-end
myofibrils
fuse to form myotubes (synthesizes proteins
characteristic of muscle fibers and
differentiates into its adult form
myoblasts
myoblasts fuse to form
________ (synthesizes proteins
characteristic of muscle fibers and
differentiates into its adult form)
myotubes
thin filaments of
actin and thick filaments of myosin
(Interdigitate in a precise
geometric relationship
sarcomere
basic functional unit of striated
muscle
sarcomere
Structure of Sarcomere includes:
*Z line / Z disk
*A band
*H zone
*M line
*I band
contains α-actinin
Z line / Z disk
-anisotropic
-interdigitated thick and thin
filaments; densest portion; strongly polarizes visible light
A band
middle of the H zone; contain enzymes that are
important in energy metabolism
M line
contains only thick filaments (myosin); lighter portion
H zone
-isotropic
-between two A bands; does not
polarize light
I band
- each myosin filament
is surrounded by six thin
filaments, and it shares these
actin filaments with
surrounding thick filaments - each actin filament is
surrounded by three myosin
filaments
region of overlap
each_____________ is surrounded by ______________, and it shares these
actin filaments with
surrounding thick filaments
- myosin filament
-six thin filaments
- each ___________ is
surrounded by __________________
-actin filament
-three myosin
filaments
- twisted actin molecules
-each has an active site where
they interact with myosin - troponin complex – complex
of 3 globular proteins;
calcium dependent switch - Resting – active site covered
by tropomyosin which is held
in place by troponin
Thin filaments
- Myosin
- Head attaches to actin
during contraction - Can only happen if
troponin changes position,
moving tropomyosin to
expose active site - myosin heads – binding
sites for ATP; form
molecular cross bridges
with actin filaments
Thick Filaments
complex of 3 globular proteins;
calcium dependent switch
troponin complex
– binding sites for ATP; form
molecular cross bridges
with actin filaments
myosin heads
-long, thin molecule (40 nm
long)
-made of 2 protein chains
forming helical filaments
Tropomyosin
globular proteins
Troponin complex
Troponin Subunits
-TnT
-TnC
-TnI
- strongly attached to tropomyosin
TnT
binds calcium ions
TnC
induces tropomyosin to move, exposing
the active site
TnI
-composed of two identical heavy
chains (long and thin), and smaller
light chains
myosin molecule
Length and width of Myosin molecule
- length : 150 nm
- width : 2 nm
Length and width of globular double “head” region
-Length: 20 nm
-Width: 4 nm
- contains enzymatic and
actin-binding activity
globular double “head” region
calcium-binding proteins
light chains
Explain Sliding Filament Hypothesis (Contraction and Relaxation)
*Muscle contracts:
-sarcomeres shorten - thin (actin)
filaments actively slid along between the
thick (myosin) filaments
-process pulls the actin filaments closer to
the center of the sarcomere, and
because the thin filaments are anchored
in the Z disks, the sarcomeres become
shorter
*Muscle relaxes or stretched
- the overlap between thin and thick
filaments is reduced, and the
sarcomeres elongate
Who proposed Sliding Filament Hypothesis?
H. E. Huxley and A. F. Huxley (1954)
- lengths of the thick
filaments and of the thin
filaments remain
constant
-filaments slide past one
another, the I band
narrows as the thin
filaments slide toward
the center of each A band
Sliding Filament Hypothesis
Sliding Filament Hypothesis: that cross-bridges are evenly distributed along each thick filament, except in the ________ where no cross-bridges are present.
bare zone
Sliding Filament Hypothesis: the force generated by a sarcomere is proportional
to the number of __________ binding myosin filaments to actin filaments
cross-bridges
Sliding Filament Hypothesis (graph): The structure of the bones and joints limits the range of movement is shown in?
plateau region of the graph
As the length of the sarcomeres
is changed, so is the amount of overlap between the actin and
myosin filaments
Length-tension relation
overlap between the thick and thin filaments
allows the largest number of cross-bridges to be formed
maximal
Sliding Filament Hypothesis (graph): When Tension drops off with increased length then _________________________________________.
thick and thin filaments overlap less and fewer cross-bridges can be formed
Sliding Filament Hypothesis (graph): drops off with decreased length is due to?
Thin Filaments colliding to one another preventing further shortening
Process of Sliding Filament Hypothesis
- A nerve signal reaches the muscle fiber, triggering the release of calcium ions from the sarcoplasmic reticulum
- Calcium ions bind to troponin molecules on the actin filaments, causing a conformational change that shifts tropomyosin, exposing the actin binding sites
- Myosin heads (cross-bridges) on the thick filaments attach to the exposed binding sites on the actin filaments.
- ATP is hydrolyzed (broken down) which provides the energy for the myosin heads to pivot and pull the actin filaments towards the center of the sarcomere, causing the filaments to slide past each other
- After the power stroke, ADP and Pi (inorganic phosphate) are released, and the myosin head detaches from the actin binding site
- When the nerve signal stops, calcium ions are actively pumped back into the sarcoplasmic reticulum, causing tropomyosin to re-cover the actin binding sites, preventing further cross-bridge formation and allowing the muscle to relax
net result hydrolysis of
one molecule of ATP
(liberating energy -
generate force)
Cross-bridge Chemistry
myosin and actin filaments associate and
dissociate in the presence of _____
ATP
*myosin acts as an _______- hydrolyzing ATP
ATPase
ATP binds to actomyosin, splitting the molecule into _____ and _______
actin and myosin
actin rebinds to the ________, increasing the rate of release (ADP + Pi)
myosin
thick and thin filaments slide
past one another driven by
changes in bonds between
_________________ and _________
myosin cross-bridges and actin
myosin heads
are not bound to actin
relaxed state
heads rotate (formation of a
series of bonds) - pulling on the
actin filament and causing it to
___________ the myosin filament.
slide past
four separate binding sites
on the myosin head
M1 to M4
Once activated myosin heads attach to ________
Actin
M1 to M2 interact in _______________ with sites
on the actln filament
sequence (left to right)
myosin head detaches only if ____ binds
ATP
2 types of Muscle Contraction
-isometric contraction
-isotonic contraction
- length of a muscle is held fixed
preventing it from shortening
isometric contraction
muscle shortens as force is
generated
isotonic contraction
smaller load
less force is generated, faster contraction
maximal isometric
tension of this muscle is
_______. Once reach it cannot shorten further
100 g
multiply the
force and the velocity
for each data point
Power-velocity curve
maximal force of 100 g, the velocity of shortening is zero (isometric); force generated by a muscle drops as its speed of shortening increases
Force- velocity curve
_____________________regulate the state of muscle contraction
free calcium ions
muscle fibers generate tension once exposed to _________________
Ca2+ and Mg-ATP
muscle fibers relax when _______ is removed, even if Mg-ATP is still present
-Ca2+
-Mg-ATP
Force increases with increasing _____________ (up to some maximum value)
Ca2+ concentration
___________ and __________
regulate binding between
myosin cross-bridges and
actin thin filaments
troponin and tropomyosin
In _______________ condition troponin complex binds with actin and tropomyosin (preventing myosin cross-bridges from binding to actin)
Low Ca2+ concentration
In an _________________ condition, troponin C binds Ca2+ changing the subunit affinities and causing the tropomyosin molecule to
move away from the myosin-binding site on actin
Increasing Ca2+
Free calcium modulates both the ___________ and __________
ATPase activity and tension
ATPase activity of myosin increases sigmoidally with the _______________ of the surrounding solution (10-8 M)
Ca2+ concentration
Mg-ATP is removed once tension has
developed
rigor mortis
when there is removal of Ca2+ and addition of
Mg-ATP
rigor is relieved
AP is propagated in a
muscle fiber, it initiates a
brief contraction, a _____
twitch
excitation-contraction coupling
occurs
latent period
Process pf Excitation-Contraction Coupling
- Action potential in a motor neuron is activated.
- This causes a postsynaptic potential in the muscle fiber
- Which gives rise to a propagated muscle AP
extensions of the plasma membrane that extend deep into the interior of each muscle fiber, associated with sarcoplasmic reticulum
Transverse tubules (T tubules)
makes intimate contact
with T tubules
sarcoplasmic reticulum (SR)
When an AP is conducted into the T tubule it causes the release of __________ stored in the neighboring sarcoplasmic
reticulum.
Ca2+ ion
How does Ca2+ get into the SR?
SR sequesters calcium
SR is capable of doing what?
- Driving the concentration of intracellular
free Ca2+ so low that contraction is prevented - remove Ca2+ from the myoplasm depends on the activity of proteins that bind and transport Ca2+ ions
- T tubule is at rest - calcium channels in the SR membrane are blocked by the “feet” of ryanodine receptors
- T-tubule membrane depolarizes - voltage-sensitive dihydropyridine receptors convey the signal to the ryanodlne receptors, and the “plungers” blocking calcium channels in the SR membrane are removed (allowing Ca2+ to flow out of the SR lumen into the myoplasm)
Plunger model
Plunger Model: free Ca2+ binds to _________, revealing cross-bridge binding
sites on actin molecules
troponin
Plunger Model: ryanodine receptors
again block the calcium channels
membrane potential returns to rest
-depolarization of the T-tubule membrane activates membrane-bound phosphodiesterase (PDE) - production of inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DG) from the hydrolysis of phosphotidylinositol
-IP3 diffuses to the terminal cisternae of the SR - binds and activates receptors causing calcium channels of the SR to open
- allows calcium ions to leak out rapidly into the sarcoplasm for contraction to occur
Enzyme- (or messenger-)mediated mechanism
What happens in the latent period?
1.initiation of an action potential in the muscle fiber,
2. propagation of the AP along the T tubules into the fiber,
3. release of Ca2+ from the sarcoplasmic reticulum
4. diffusion of the Ca2+ ions to troponin molecules
5. binding of Ca2+ to troponin
6. activation of myosin cross-bridges and their binding to actin thin filaments, and generation of force
______________ by myosin cross-bridges as they cyclically attach to and detach from actin thin filaments
Hydrolysis of ATP
ENERGETICS OF MUSCLE CONTRACTION
-Hydrolysis of ATP by myosin cross-bridges
-Pumping of Ca2+ during excitation-coupling
-Direct Phosphorylation
-Anaerobic Glycolysis
-Oxidative Phosphorylation of ADP
- high energy phosphates are
transferred from creatine
phosphate to ADP,
regenerating AT
direct phosphorylation
hydrolyzes glucose,
dephosphorylating ADP in the
process (lactate as byproduct)
anaerobic glycolysis
regenerates ATP
oxidative phosphorylation of ADP
Classification of Skeletal Muscle Fibers
-oxidative or glycolytic fibers, (by the source of ATP)
- fast-twitch or slow-twitch fibers, (by the speed of muscle contraction)
Slow and fast oxidative fibers rely on _______ and _________
glucose and oxygen
Fast glycolytic fibers rely on ______________
anaerobic glycolysis
Muscles incur _____________ during anaerobic glycolysis
oxygen debt
-contract very slowly and do not produce twitches
-found in the postural muscles of amphibians, reptiles, and birds, muscle spindles and extraocular muscles of mammals
-normally do not produce APs and they do not require an AP to spread excitation (innervating motor neuron runs the length of the muscle fiber and makes repeated synapses all along)
-myosin cross-bridges attach and detach very slowly (extremely slow shortening velocity and ability to generate isometric tension very efficiently)
Tonic Muscle Fiber
-contract slowly and fatigue slowly
- they are found in mammalian postural muscles.
-They are characterized by a slow-to-moderate V, and slow Ca2+ kinetics.
-They generate all-or-none APs, so they contract in response to motor neuron input with all-or-none twitches.
-Like other twitch fibers, they typically
have one or at most a few motor endplates
Slow twitch (or type I) fibers
-for slow, sustained contractions without fatigue
-contain extensive blood supply
-high density of mitochondria
-abundant stored myoglobin (protein that binds oxygen more tightly than hemoglobin does)
-important in maintaining posture in terrestrial
vertebrate
slow oxidative fibers (red muscles)
Two kind of Fast fibers
-fast glycolytic fiber (white muscles)
-fast oxidative fiber
-lacks efficient blood supply
-pale in color
-function anaerobically
-fatigue rapidly
fast glycolytic fiber (white muscles)
-extensive blood supply
-high density of mitochondria and myoglobin
-function aerobically
-for rapid, sustained activities
fast oxidative fiber
Types of stimulations according to strength
➢ subthreshold
➢ threshold
➢ submaximal
➢ maximal
➢ supramaximal
not capable of inducing a response or muscle
contraction
subthreshold
- weakest stimulus capable of causing contraction
threshold
intermediate between threshold and supramaximal
submaximal
causes a maximal contraction wherein the overlap between the myofilaments is greatest
maximal
- beyond maximal stimulus
- no higher contractions are observed because all the
motor units have been activated.
supramaximal
➢ A twitch results from a single action potential in a motor
neuron
➢Single stimulus-contraction-relaxation sequence
in a muscle fiber
➢Varies in duration
Muscle Twitch
graph of tension development in
various muscles during a twitch contraction
myogram
Muscle Twitch is divide into:
-Latent Period
-Contraction phase
-Relaxation Phase
– starts at stimulus
– action potential sweeps across the sarcolemma and the sarcoplasmic reticulum releases calcium ions
– muscle fiber does not produce tension,
contraction has yet to begin
Latent period
– tension rises to a peak
– calcium ions bind to troponin, active sites on thin
filaments are being exposed, and cross-bridge
interactions are occurring
Contraction Phase
– calcium levels are falling, active sites are being
covered by tropomyosin, and the number of active
cross-bridges is declining
Relaxation phase
Contraction of a whole muscle is ______, which
means that the extent and strength of its
contraction can be voluntarily altered
graded
two basic mechanisms by which the
nervous system produces graded contractions:
– Varying the number of fibers that contract
– Varying the rate at which fibers are stimulated
Muscle curves showing increasing amplitudes with increasing ____________
electrical intensity
– Ger., ‘staircase’
– Gradual increase in muscular contraction due to rapidly
repeated stimulation
– Occurs when muscle is stimulated a second time
immediately after relaxation phase has ended
– First 30-50 stimulations
– Rise in tension due to increase of Ca2+ in the sarcoplasm
– Eventual depletion of chemical energy leading to fatigue
→ decreasing amplitude of muscle contraction
Treepe
➢ Prolonged and strong contractions of the muscles
often lead to a familiar state called muscle fatigue.
➢ the rate of depletion of muscle glycogen = to the
increase in muscle fatigue.
➢ Hence, fatigue results mainly from the inability of the
contractile and metabolic processes of muscle fibers
to continue supplying the same work output.
Fatigue
Interruption of blood flow through a contracting muscle leads to almost complete ____________. This occurs usually within a minute or two, because of the low nutrient supply and the loss of oxygen.
muscle fatigue
Larger number of motor units stimulated, the greater effect of ___________.
contraction
A smooth and steady increase in muscle tension is produced by increasing the number of motor units brought into play
motor unit recruitment
____________ of multiple motor neurons results in stronger contractions
Recruitment
A twitch results from a __________________ in a motor neuron
single action potential
More rapidly delivered action potentials produce a graded contraction by ________________
summation
➢ sustained
contraction of a muscle
brought about by the
application of a large number
of stimuli in rapid succession
leaving insufficient time for
relaxation.
➢The height of tetanic
contraction is greater than
the twitch produced by single
stimulation of the same
intensity because of the
summation of twitches
Tetanus
Classification of Tetanus
-Incomplete Tetanus
-Complete Tetanus
periods of incomplete relaxation take
place between the summated stimuli.
Incomplete tetanus
-no relaxation occurs between stimuli
-the tension developed is about
four times that developed by the individual twitch contractions.
Complete Tetanus