Unit 3 Muscles Flashcards
what is muscle?
tissue specialized to convert biochemical reactions into mechanical work
what do muscles generate?
- motion
- force
- heat and contribute to homeostasis (temp)
what are the 3 types of muscle
- skeletal
- cardiac
- smooth
general description of skeletal muscles
-attached to the bones of the skeleton
-control body movement
-contract in response to signal from somatic motor neuron
-cannot initiate contraction on its own
-striations
general description of cardiac muscle
-found only in the heart
-pump to move blood around the body
-striations
general description of smooth muscles
-primary muscle of internal organs and tubes
-influences movement of materials through the body
-no striations
characteristics of skeletal muscles
-responsible for positioning and movement of skeleton
-make up about 40% of body weight
-attached to bones via tendons
-tendons are composed of dense regular connective tissue (collagen)
Gross structure of skeletal muscles
-outer connective tissue (epimysium)
-contains bundles of muscle tissue called fascicles
-fascicles are covered by the perimysium and contain nerves and blood vessels
-muscle fibres/cells are found in each fascicle
muscle fibres
-covered by an innermost connective tissue sheath (endomysium)
-within the muscle fibres are the functional units of skeletal muscle (myofibrils)
-contain so many myofibreils that there is little room for other organelles
-cytosol contains many glycogen granules (energy storage) and mitochondria for ATP synthesis
structure of a muscle fibre
-long cylindrical cell
-several hundred nuclei on the surface of the fibre
-cell membrane is called the sarcolemma
-majority of space is taken up by myofibrils (contractile and elastic protein bundles)
-contain a specialized endoplasmic reticulum called the sarcoplasmic reticulum
-associated with the sarcoplasmic reticulum is a series of branching tubes (t-tubules/ transverse tubules) which the lumen is continuous with the ECF
-the t-tubules are closely associated with terminal cisternae which sequester calcium
-a t-tubule with flanking terminal cisternae are called triads
-t-tubules allow for rapid action potential diffusion into the muscle fibre
general terms vs muscle equivalent
- muscle cell –> muscle fibre
- cell membrane –> sarcolemma
- cytoplasm –> sarcoplasm
- modified endoplasmic reticulum –> sarcoplasmic reticulum
structure of a myofibril
-occupy most of the space in a muscle fibre
-highly organized and consist of bundles of contractile elastic proteins
1. Contractile proteins (generate movement)
-actin
-myosin
2. regulatory proteins
-tropomyosin
-troponin
3. accessory proteins
-titin
-nebulin
what is a sarcomere
-one repeated pattern of the stripes in muscles (striations)
what is the sarcomere made of?
- Z-line (disks)
-zwischen (german for in between) - I band
-isotropic
-reflects light uniformly - A band
-anisotropic
-scatters light unevenly - H zone
-part of the A band
-helles (german for clear) - M line
-mittel (german for middle)
what causes the striations?
organization of myofibril protein components (actin and myosin) cause striations
what is myosin
-a motor protein that consists of two coiled protein molecules that have two important parts (head and tail)
-head and tail are joined by flexible hinges
-abount 250 myosin filament are joined together as the thick filament
-arranged so that the heads are at the ends and the tails are all together
what is actin
-composed of G-actin subunits (globular actin)
-g-actin form a chain called f-actin (filamentous actin)
-two f-actin chains twist together to form the basis of the thin filament
-associates with regulatory proteins to form the thin filament
-myosin head interacts with actin filaments called a cross bridge
what are the regulatory proteins and their purpose on actin filaments
-troponin and tropomyosin
-regulate muscle contraction
purpose and structure of the z-line
-site of attachment for thin filaments
-one sarcomere is made up of two z discs and the filaments between them
purpose and structure of the I band
-region containing only thin filaments
-z disc runs through the middle of an I band
-each half of the I band is part of a different sarcomere
purpose and structure of the A band
-region containing thick and thin filaments
-think and thin filaments overlap at the outer edges of the A band
-center has only thick filaments
purpose and structure of the H zone
-part of the A band
-region containing only thick filaments
-center region is lighter than the outer edges
purpose and structure of the M line
-site of attachment for the thick filaments
-center of the sarcomere
what is titin and its purpose
-largest known protein
-elastic protein
-stretches from one Z disc to M line in a sarcomere
-stabilizes position of contractile filaments
-returns stretched muscles to their resting length
what is nebulin and its purpose
-non elastic
-attaches to the z disc
-helps align actin filaments in the sarcomere
how do the actin filaments move?
thin filaments are pulled along by the heads of the myosin molecules. The heads “walk” along the thin filaments, but since the myosin is fixed, the thin filaments move
what are the steps in cross bridge cycling
Step 1
-myosin is tightly bound to actin (rigor state)
-ATP binds to the myosin head
-myosin releases from actin
Step 2 (most relaxed muscles are here)
-myosin ATPase activity hydrolyses ATP
-ADP + Pi which causes the myosin head to swing over and binds weakly to new actin molecule, 1-3 molecules away from the initial
-now at a 90° angle
Step 3
-Pi released
-myosin head rotates on hinge, swings back, pulling actin along with it towards the M line
-this is called the power stroke
Step 4
-ADP is then released
amount of crossbridge cycling during a contraction
-not all cross bridges move simultaneously during a contraction
-about 50% are attached and produce a contraction
what would happen if all the crossbridges released together
thin filaments would slip back into their original positions and the contraction would not occur
what stops muscles from contracting whenever ATP is available
the actin filament is associated with two regulatory proteins that control this
how does tropomyosin work?
-coils around f-actin molecules and can cover and uncover each G-actin molecule in the strand
-when it covers the G-actin, it blocks the myosin binding site
-at rest tropomyosin is in the off position (coving the binding site) which prevents contraction
-position is regulated by troponin
how does troponin work?
-three subunits, one is called troponin C
-calcium binds to troponin C which causes a conformational change in troponin
-the conformational change causes the tropomyosin to the on position so that myosin can bind to actin
how does concentrations of calcium regulate muscle contraction?
High levels: contraction
Low levels: relaxation
what is excitation contraction coupling
-series of electrical and mechanical events in a muscle which leads to muscle contraction-occurs through an action potential in the muscle membrane
-skeletal muscles only contract when stimulated by a signal from the nervous system.
what are the steps of a skeletal muscle contraction
- ACh is released by the neuron into synaptic cleft at the neuromuscular junction and binds to nicotinic cholinergic receptors on motor end plate
- The receptors are Na+/K+ channels
- The binding of ACh opens the channels –> both Na+ & K+ move across the membrane
- ACh is removed by acetylcholinesterase
- Na+ influx exceeds K+ efflux –> local
depolarization occurs at the synapse
(called an End Plate Potential - EPP) - The end plate potential (action potential) then moves down the T-tubule system
- T-tubule membrane contains
dihydropyridine receptors (DHP receptors) –> L-type calcium channel
- Depolarization changes the conformation of the DHP receptors
- DHP receptors are mechanically linked to the Ca2+ channels of the SR known as ryanodine receptors –> RyR - DHP receptor then changes RyR
conformation which results in the opening of SR Ca2+ channels –> Ca2+ leaves the SR
- This increases cytosolic [Ca2+] - Ca2+ binds to troponin –> moves
tropomyosin out of the way - Myosin completes powerstroke
- Actin filament slides towards the M line –> contraction
- Relaxation of skeletal muscle occurs when
C2+ is pumped back into SR through the Ca2+-ATPase - decrease Ca2+ in cytosol causes troponin and Ca2+ to unbind
- Tropomyosin goes into the “off” position and covers binding site
- Elastic elements pull filaments back to the relaxed position when myosin unbinds
EPPs and threshold
EPPs are essentially always above threshold which results in a contraction
general info about energy and muscle contraction
- Muscles convert biochemical energy into mechanical work
- Ca2+ controls muscle contractions –> removed from the cytosol by Ca2+-ATPase
- Na+ and K+ ions are pumped back into/out of the cell using ATP > how???
- Myosin:Actin interaction uses ATP
ATP and muscle contractions
- ATP is the main energy currency of the cell (ATP is a nucleotide triphosphate)
- Muscle contraction requires a steady supply of ATP
- Energy is transferred from nutrients –> ATP
- Occurs aerobically or anaerobically
- Glycolysis occurs in the presence (aerobic) or absence (anaerobic) of oxygen
- Provides limited amount of ATP per mole of glucose used –> 2 ATP
- Generates unwanted metabolites in absence of oxygen –> lactic acid
- Oxidative metabolism requires oxygen present (comes from the air you breath)
- Provides up to 15X more ATP per glucose molecule
- Does not produce toxic end products
- Oxidative metabolism provides most of the energy required for muscle contraction when oxygen is available (need mitochondria)
Phosphocreatine and muscle contraction
- Phosphocreatine is a high energy phosphate molecule (In addition to ATP)
- Muscles have a high concentration of phosphocreatine
- Provides a rapid source of energy for the muscle
- Easily donates the inorganic phosphate to ADP to create ATP –> provides a limited supply of ATP
- Used mainly to buffer [ATP] over very short time scales (i.e. seconds)
- Reaction: phosphocreatine + ADP –> ATP + creatine
- Catalyzed by creatine Kinase (CK)
- Muscles contain large amounts of CK
- Resting muscles store energy in phosphocreatine
what is twitch and latent period?
a. Twitch –> single contraction-relaxation cycle
b. Latent period –> short delay between the AP & the beginning of the muscle tension
- This is the time it takes for excitation-
contraction coupling to occur
what are the three types of muscle fibers
- Slow-twitch oxidative fibres (type I)
- Fast-twitch oxidative-glycolytic fires (type IIA)
- Fast-twitch glycolytic fibres (type IIX)
what is oxidative or glycolytic
- Oxidative or glycolytic refer to the primary sources of ATP
- Oxidative fires usually appear red due to the presence of myoglobin
- Myoglobin –> an oxygen-carrying haeme protein
- Oxidative fibres are smaller than glycolytic fires, have numerous mitochondria & are better vascularized –> more blood vessels
what is fast or slow
- Fast or slow refers to the rate of myosin ATPase activity
- Fast fibres can split ATP more quickly and can contract/develop tension faster
- Result of the presence of different isoforms of myosin
- The length (duration) of contraction also varies between fibres
- Fast fibres have a shorter twitch (they can have more twitches per unit time)
- Twitch duration is determined by the rate of removal of Ca?+ from the cytosol
- This sets the speed at which the muscle relaxes
- Short twitch duration is useful for rapid, small muscle contractions (e.g. playing the piano, typing)
- Long twitch duration good for long sustained movements (lifting heavy loads)
Which type of muscle has the highest rate of Ca2+ removal from the cytosol?
Fast twitch muscles
resting fiber length
- The tension exerted by a muscle during a single twitch is influenced by:
1. The muscle type (because of their structure, fast twitch fibres can generate more tension)
2. Sarcomere length at the start of contraction - Sarcomere length is the degree of overlap between the
thick and thin filaments
a. Too little overlap - Few crossbridges
- Little force can be generated
b. Too much overlap - Actin filaments start to interfere with each other
- Less force generated
c. Way too much overlap - Thick filaments collide with Z disk
- Force rapidly decreases
force of a muscle contraction
- A single twitch does not represent the maximum force the muscle fibre can develop
- Force of a muscle fibre can be increased by increasing the rate of action potentials that stimulate the fibre
what is summation
- Increase in force generated by a muscle
- Due to repeated stimulation from action potentials that occur before the muscle has fully relaxed
what is tetanus
- Term for the state of a muscle when it reaches maximum force of contraction
1. Incomplete (unfused) tetanus - Slow stimulation rate –> fibre relaxes
slightly between stimuli
- Complete (fused) tetanus
- Fast stimulation rate –> fibre does not
have time to relax
- fatigue causes muscle to lose tension
despite continuing stimuli
what is a motor unit
- The motor unit is the basic unit of contraction in an intact skeletal muscle
- A muscle is made up of many different motor units
- A motor unit is composed of two components:
1. A group of muscle fibres -> # of fibres varies
2. The somatic motor neuron that controls them - All muscle fibres are of the
same skeletal muscle fibre type - Fast-twitch motor units
- Slow-twitch motor units
- An action potential in somatic
motor neuron –> contraction of ALL
muscle fires in each motor unit - Each motor unit contracts in an all-or-none fashion
how can contraction be varied
- Changing the type of motor unit that is activated
- Changing the number of motor units that are active
- Recruitment:
- Force of contraction of a muscle is increased by using more motor units
- Different muscle fires are recruited at different times
- Slow oxidative fibres have a low threshold for stimulation
- Fast glycolytic fires have a high threshold for stimulation
Which will have more muscle fibres per motor unit, those involved in fine movements or those used for coarse movements?
Coarse
what are the two main types of muscle contraction
- ISOTONIC
- Creates force and moves a load
- The load is usually constant, and the
muscle length changes - ISOMETRIC
- Creates force without movement
- Muscle length is constant
- The load is usually greater than the force that can be applied
How can an isometric contraction create force if there is no change in muscle length?
Even though sarcomeres shorten, muscle length stays constant because these elastic elements stretch to take up force until fully stretched
where is smooth muscle found in the body
- Walls of hollow organs & tubes –> not attached to bones of skeleton
- Fewer in terms of % body weight, but much more important
- Some important smooth muscles –> bladder sphincter, intestine, walls of blood vessels
how is smooth muscle arranged
- Smooth muscle can be arranged in two different ways:
1. Single unit –> cells coupled by gap junctions - Not necessary to electrically stimulate each individual fibre
- Found on walls of internal organs –> e.g. blood vessels
2. Multi-unit –> no gap junctions - Each individual muscle fibre is separately innervated
- e.g. iris of the eye, parts of reproductive organs
what are the differences between smooth and skeletal muscle
a. On whole muscle level:
1. Contraction of smooth muscle changes muscle shape, not just length
2. Smooth muscle develops tension (force) slowly
3. Smooth muscle can maintain contraction longer without fatiguing –> important because some are contracted most of the time –> e.g. internal bladder sphincter
b. On cellular level:
1. Fibres much smaller in smooth muscle than skeletal muscle fibres
- About same diameter as a single myofibril in a skeletal muscle fibre
2. Actin & myosin are not arranged into sarcomeres
- Thus, no banding pattern (no striations)
3. Actin & myosin arranged in long bundles diagonally around periphery of the cell
4. Actin anchored at cell membrane structures called dense bodies
- Not attached to the Z lines as in skeletal muscle
5. No T-tubules in sarcolemma, not much sarcoplasmic reticulum (SR)
- Smooth muscle cells have special vesicles called caveolae that are invaginations of the sarcolemma that are specialized for cell signalling
6. Force of contraction is related to amount of Ca2+ released
c. On molecular level:
1. Less myosin per unit actin in smooth muscle than skeletal muscle
2. Actin and myosin filaments are longer and overlap more in smooth muscle
3. Myosin ATPase activity much slower in smooth muscle
4. Myosin heads are located along all parts of myosin molecule in smooth muscle
5. No troponin in smooth muscle
what is the effect of not having t-tubules?
no direct coupling of the action potential to Ca2+ release from the SR through DHP receptor-ryanodine receptor coupling as in skeletal muscles
-instead Ca2+ entering through the cell membrane causes Ca2+ release from the SR
How do these properties of myosin contribute to the characteristics of the smooth muscle as a whole?
Contract more slowly & for longer periods of time than skeletal or cardiac muscle
- In part this is due to slower myosin ATPase activity
- Longer actin and myosin filaments allow longer contractions and allow smooth muscle to be stretched yet still be able to contract
-Remember: in skeletal muscle too much stretching leads to too little overlap and an inability to contract
- What would happen if your bladder were lined with muscle organized in sarcomeres?
- bladder would stretch as it fills up
- if it stretches too much it would not be able to contract again
what is the role of Ca2+ in contraction in smooth muscles
- Major difference between contraction of smooth muscle & cardiac muscle is the role of phosphorylation in regulating the smooth muscle contraction process
what are the steps of smooth muscle contraction
- Signal to initiate contraction is increase in cytosolic Ca2+
- Cytosolic Ca2+ levels control contraction
- Ca2+ enters from extracellular fluid (ECF) through:
- Voltage gated channels –> open when cell depolarizes
- Stretch activated channels –> open
when membrane stretched
- Chemically gated channels –> open in
response to hormones
-Ca2+ entry from the ECF results in
release of SR Ca2+ and Ca2+ from
caveolae - Ca2+ binds to calmodulin (CaM) in the cytosol
- Ca2+/CaM activates the enzyme myosin light chain kinase (MLCK)
- MLCK activates myosin by phosphorylating the light chain of the myosin molecule in the head using energy and Pi from ATP –> this ATP is used to activate the myosin through
phosphorylation (not for crossbridge
cycling)
-when myosin is not phosphorylated, ATPase activity id blocked
-when myosin is phosphorylated, ATPase is active - The phosphorylated myosin (active) can now interact with actin and go through crossbridge cycling and allow contraction to occur in the smooth
muscle cell –> remember,
additional ATP is needed for each crossbridge cycle - MLCK uses the Pi from ATP to activate myosin (turn it “on”), but additional ATP is needed to go through crossbridge cycling for contraction to occur.
regulation of smooth vs skeletal muscles
Smooth:
-myosin is regulated via phosphorylation of myosin
Skeletal:
-actin is regulated via troponin and tropomyosin interaction
what would happen to contraction if a smooth muscle cell where placed in a Ca2+ free saline solution
-no contraction
-no Ca2+ entry from the extra-cellular environment
relaxation in smooth muscle
- Relaxation is a multi-step process:
1. Ca2+ is removed from the cytosol - Pumped back into the SR using ATP to
the extra-cellular environment through Ca2+ - Na+ anti-port, Ca2+-ATPase
- Decrease in Ca2+ levels in the cytosol
causes Ca2+ to unbind from calmodulin –> Inactivates MLCK
- Myosin light chains are dephosphorylated –> By myosin light
chain phosphatase (MLCP)
- Dephosphorylation of myosin does not automatically relax the muscle
- This allows the smooth muscle to enter the latch state –> not fully understood
- Tension is maintained (myosin remains bound to actin) but with minimal ATP consumption
Structure of cardiac muscles
- Cardiac muscle cells are called myocardial cells > these are specialized muscle cells of the heart
- Shares features with both smooth and skeletal muscles
- Most myocardial cells are typical striated muscle
- Contractile fires organized into sarcomeres
- Cardiac muscle differs from skeletal muscle:
a. Cardiac muscle cells are much smaller with single nucleus with about 1/3 of the cell volume is occupied by mitochondria
b. T-tubules are much larger and branched and the sarcoplasmic reticulum (SR) is smaller
c. Adjacent cells are joined by intercalated discs with desmosomes - About 1% of cardiac muscle cells are NOT involved in contraction - autorhythmic/pacemaker cells
- They are involved in the electrical excitation of the heart –> known as the electrical conducting system of the heart
- They initiate heartbeat & allow the electrical excitation to spread rapidly throughout the heart
- They are connected to other cardiac cells via gap junctions
how does cardiac muscle contract
- Like skeletal muscle contraction EXCEPT:
- Ca2+ enters through Ca2+ channels on cell membrane as well as the SR
- First: calcium enters through external Ca2+ channels
- Next: calcium-induced calcium release –> release of stored Ca2+ from SR
- SR calcium provides about 90% of that needed for contraction - Cardiac cells have a Na+/Ca2+ antiport (in addition to Ca2+-ATPase)
- Removes Ca2+ from cytosol and pumps it into the extracellular space - Exhibit graded (not all-or-none) contraction –> the force generated is
proportional to number of active crossbridges
- Number of active crossbridges is proportional to cytosolic [Ca2+]
- Therefore, the force generated is proportional to cytosolic [Ca2+]
what are the factors that influence cardiac muscle contraction force
- Changes in [Ca2+] in cytosol
-Regulated by epinephrine & norepinephrine –> bind to & activate beta 1-adrenergic receptors
-Binding then activates cAMP second messenger signalling pathway that leads to:
a. Phosphorylation of voltage-gated Ca2+ channels
- Increases the probability of the channel to open –> increase [Ca2+] in the cytosol
b. Phosphorylation of phospholamban
- Leads to increase SR Ca2+-ATPase activity –> increase SR Ca2+
* Over all results in
more forceful contraction and a shorter
duration of contraction - Sarcomere length
- Tension generated is proportional to the length of muscle fibre
- Due to degree of overlap between actin and myosin –> there is an optimal amount of overlap
- Note that stretching a myocardial muscle cell may also allow more Ca2+ to enter through cell membrane Ca2+ channels –> contributing to a more forceful next contraction
what are the steps in cardiac muscle contraction
- Cardiac muscle is also an excitable tissue –> can generate action potentials
- Major sequence of events:
Phase 4: resting membrane potential
Phase 0: depolarization –> The AP opens voltage-gated Na+ channels, causing a rapid increase in membrane Na+ permeability (close again)
Phase 1: initial repolarization –> open fast K+ channels allow initial repolarization
Phase 2: the plateau –> initial depolarization triggered voltage-gated Ca2+ channels to slowly open, causing an increase in Ca2+ permeability and the fast K+ channels close
Phase 3: rapid repolarization –> the Ca2+ channels close and the slow voltage-gated K+ channels open (initial depolarization was the trigger), and the resting stage ion permeability is restored (phase 4)
why is sustained depolarization happening and what are its results
- Sustained depolarization is due to the slow opening of the voltage-gated Ca2+ channels
- Result of sustained depolarization:
- Typical action potential in neuron or skeletal muscle cell: 1-5 msec
- Typical action potential in cardiac muscle: >200msec
why is sustained depolarization important
Prevents tetanus and allows the heart to relax between contractions a it needs to last a while
Why don’t cardiac muscle cells undergo summation and tetanus?
Because of the longer refractory period –> means that the cell has finished contracting before the next action potential
