Lecture 8 and 9 Flashcards
What are the 3 types of muscles?
smooth, cardiac and skeletal muscle
Smooth muscle
Smooth muscles mainly line hollow organs such as the gut or blood vessels and are not under voluntary control
Cardiac muscle
Located only in the heart, it generates force to pump blood around the body and is not under voluntary control
Skeletal muscle
Applies force to the bones to control posture and body movements. It is under voluntary control and is also known as striated muscle (striped) or voluntary muscle.
Able to influence joint movement and position.
Skeletal muscle’s main function is to give rise to movement (turning ATP into mechanical energy) by the development of force by the shortening of muscle.
Skeletal muscle produces force…what is this force used for?
Force generated is mainly used to move and to resist movement of joints (posture).
How does a muscle develop a force?
Muscles develop force in only one direction, that is they can ‘pull’ (develop force by shortening), but they cannot ‘push’ (develop force by actively lengthening) as the joint does not allow for this movement
Other secondary jobs of the skeletal muscles
Provides support and protection for soft internal organs especially the muscles of the abdominal wall
Provides voluntary control over major openings that allow passage of substances into or out of the body.
Converts energy (in part) to heat which is used to maintain core temperature (e.g. shivering)
Provides a major ‘store’ for energy and protein.
Communication (e.g. facial expression)
A muscle fibre is a ….
single cell
Structural features of skeletal muscles
Skeletal muscle fibres are huge multinucleate cells containing large amounts of protein
Connectives tissues ensheath the muscle fibres, and connect fibres to the bones
Richly supplied the blood vessels
Richly supplied with nerve fibres
Skeletal muscle fibres are huge multinucleate cells…. what does multinucleate means?
Lots of nuclei
Fascicles
A bundle of skeletal muscle fibres surrounded by perimysium, a type of connective tissue.
Muscle fibres are gathered into bundles called fascicles.
Muscles
Fasicles are bundled into bundles called muscles.
A muscle is a group of muscle tissues which contract together to produce a force.
Fibres, fascicles and muscles are each ensheathed in…
Connective tissue …
Theendomysiumis the connective tissue that surrounds each muscle fibre (cell).
Theperimysiumencircles a group of muscle fibres, forming a fascicle.
Theepimysiumencircles all the fascicles to form a complete muscle.
Deep fascia
The deep fascia covers muscle and it is made out of DFCT
Connective tissue investments are gathered together to form …
Tendons (It extends beyond the muscle tissue to connect the muscle to a bone or to other muscles .)
The connective tissue coverings (the deep fascia, epimysium, perimysium and endomysium) all come together to form the tendon.
Tendon
Connect muscle to bone
Myofibril
Actin and myosin filaments are bundled together in groups called myofibrils
Myofibrils are long filaments that run parallel to each other to form muscle fibres. Myofibrils are made up of repeating subunits called sarcomeres.
Describe what a muscle is made up of (basic)
Muscle is attached to bone by tendons, and then we go down further, we have a single muscle fibre within the muscle and the muscle fibre is composed of multiple myofibrils. Fascicles are bundled into bundles called muscles. Fascicles are a bundle of SM fibres.
Epimysum
Connective tissue that encircles all the fascicles to form a complete muscle.
Endomysium
Connective tissue that surrounds each muscle fibre (cell)
Perimysium
Connective tissue that encircles a group of muscle fibres forming a fascicle.
Myoblasts
Myoblasts are the embryonic precursors of myocytes
Sarcolemma
The plasma membrane around a muscle cell.
How are muscle fibres formed?
During development muscle precursor cells (myoblasts) fuse together to form large multinucleate cells enclosed by a single common cell membrane (sarcolemma). Each muscle fibre therefore has hundreds to thousands of nuclei.
Average diameter and length of muscle fibres
Fibres are typically about 20-40 μm (micrometres) in diameter, but can be many cm long
Myotube
A skeletal muscle fibre formed by the fusion of myoblasts during a developmental stage.
What does the specific arrangement of proteins in the cytoplasm give the muscle the ability to do?
Allows the muscle to have the ability to develop physical force in response to electrical signals from the brain
Myofibres
A multi nucleated single muscle cell
Myofilaments
Myofilaments are the filaments of myofibrils, constructed from proteins, principally myosin or actin. Gives skeletal muscle its characteristic striated/striped appearance (bands of thick and thin filaments along the length of the fibre)
Two main proteins of the myofilaments are…
Actin (thin filaments) and myosin (thick filaments)
Actin
A protein which forms (together with myosin) the contractile filaments of muscle cells, and is also involved in motion in other types of cell
Actin filaments are the smallest cytoskeletal filaments, with a diameter of 7 nm. They are thin, relatively flexible threads that can be cross-linked together in different ways to form very different structures. Actin monomers are called globular actin or G-actin. As their name suggests, they are fairly globe-shaped in structure. At the right concentration of monomers, they can polymerize head to tail to form filamentous actin or F-actin. F-actin threads associate with each other in a thin double-helical structure. Associated with each thin filament is a pair of strands of tropomyosin that attaches to the actin at regular sites via the binding at regular intervals of the globular protein, troponin. Troponin binds tropomyosin and actin, and has an additional important role in regulating interaction between actin and myosin during the working cycle. Troponin is attached to the protein tropomyosin and lies within the groove between actin filaments in muscle tissue. Some calcium attaches to troponin, which causes it to change shape, exposing binding sites for myosin (active sites) on the actin filaments.
What are the thin filaments of the muscle?
Actin
Myosin
The thick filament is primarily myosin. The myosin molecule has a long thin tail and globular head. The thick filament is formed from arrays of parts of myosin molecules arranged with the tails pointing towards the M-line and forming a complex double headed structure. The heads of the various myosin pairs form a spiral, each facing one of the six surrounding thin filaments (recall the hexagonal array of thick and thin filaments of the myofibril) The globular head of the myosin has an ATP binding site and has ATPase activity (it can hydrolyse ATP to ADP+Pi, releasing energy in the process)
What are the thick filaments of the muscle?
Myosin
How are thick and thin myofilaments arranged?
Arranged in a regular hexagonal array when seen in cross section (each thick filament is surrounded by 6 thin filaments)
Sarcomere
The myofilaments are arranged in a regular pattern along the length of the muscle fibre in repeated units known as sarcomeres. The sarcomere is in charge of producing force.
Transverse tubules (T-tubules) and what is their job?
Transverse tubules (T-tubules) are tubular extension (invagination) of the surface membrane that runs from the cell surface deep into the fibre in a regular array. Function is to conduct impulses from the sarcolemma down into the cell and, specifically, to another structure in the cell called the sarcoplasmic reticulum.
Terminal cisternae
Enlarged areas of the sarcoplasmic reticulum surrounding the transverse tubules.
Triad
A terminal cisternae of the SR, a transverse tubule and another terminal cisternae of the SR, you make up a structure called a triad.
The sarcoplasmic reticulum contains what ion and what is it used for?
Calcium and it is required for force production
Describe sarcolemma in depth
The sarcolemma (specialised plasma membrane), what makes it specialised is that it invaginates down into the cell (extremely unique to muscle cell). A large amount of this membrane penetrates into the cell which is important for converting electrical signals which allows you to produce force. Their structures allow the stimuli for the contraction to get thrown down into the cell to allow all the repeating units to be contracted in sync.
Sarcoplasmic reticulum and what is its job?
SR is a specialised version of the ER. The SR is an extensive membranous tubular network associated precisely with the T-tubules at regular intervals. The job of the SR is to take up and store calcium, then to release calcium into the cytoplasm on receipt of an action potential conducted along the associated T-tubules
G actin vs F actin
Actin exists in two forms: G-actin (or globular actin) and F-actin (or fibrous actin). G-actin has one ATP binding site per monomer. F-actin is a filamentous polymer, composed of G-actin monomers.
M-line
M line is the attachment site for the thick filaments. The M line is in the centre of the sarcomere.
Z-line
Any of the dark bands across a striated muscle fibre that mark the junction of actin filaments in adjacent sarcomeres.
Tropomyosin
Tropomyosin is a major regulatory protein of contractile systems and cytoskeleton, an actin-binding protein that positions laterally along actin filaments and modulates actin–myosin interaction.
The tropomyosin is a long stand that has troponin molecules along it at regular intervals
Troponin
Troponin is the sarcomeric Ca2+ regulator for striated muscle contraction. On binding Ca2+ it transmits information via structural changes throughout the actin-tropomyosin filaments, activating myosin ATPase activity and muscle contraction.
Difference between troponin and tropomyosin
Troponin and tropomyosin are two proteins which regulate sarcomere contraction via calcium binding. The key difference between troponin and tropomyosin is that troponin frees the myosin binding sites of actin filaments while tropomyosin blocks the binding sites.
What is associated with each thin filament?
A pair of stranded of tropomyosin that attaches to the actin at regular sites via the binding at regular intervals of the globular protein, troponin.
What is the sliding filament theory?
The contractile proteins develop force by triggered molecular interaction that allows association of the myosin head with the nearby thin actin filament followed by the flexing of the myosin head to allow it to ‘walk’ along the thin filament. In this process the interlaced thick and thin filaments slide past one another. The arrangement of the myosin heads in a sarcomere means that when this process is activated, the ends of the sarcomere are drawn closer together by the flexing of the myosin heads (the sarcomere Z-lines are drawn closer to the central M-line)
What is the Motor Unit?
A motor neuron and all the muscle fibres it controls is called a motor unit. Remember that each muscle fibre is innervated by only one axon, but axons can have multiple branches to the different fibres
Motor neuron cell bodies are in the ventral/anterior part of the spinal cord. Motor axons project out of the spinal cord to form ventral nerve roots and eventually to form spinal nerves. Axons project together to the target muscle, in the muscle they branch so that each axon innervates many fibres, though each fibre is contacted by only one axon. A whole muscle, therefore, is a collection of motor units.
What does the size of motor units affect?
Big motor units (hundreds of fibres) generate more force however they do not provide much control over small increments in force, for example in your leg muscles.
Smaller motor units (less than 20 fibres allow for fine control but they do not develop much force for example in the muscle located in your hand
Muscle contractions are triggered by…
Electrical events (action potentials)
Where do action potentials arise?
Action potentials in the spinal cord motor neurons are …?
Arrival of action potential at the NMJ initiates…?
Action potential in the muscle fibre triggers…?
Action potentials arise in the brain and are conducted out of the CNS along motor neurons in the spinal cord. Action potentials in the spinal cord motor neurons are conducted out of the CNS along motor axons to muscle fibres. Arrival of action potential at NMJ initiates synaptic transmission which results in generation of action potentials in post synaptic muscle fibre. Action potential in muscle fibre triggers a process known as excitation contraction coupling that results in the development of force within the fibre.
Neuromuscular junction
The area where the axon touches the muscle is called the neuromuscular junction (NMJ).
The myelinated axon of a motor neuron terminates at a single point on the muscle fibre. This specialised synapse is the NMJ. Each muscle fibre receives contact from one motor neuron at one site, to form an excitatory synapse. Each motor neuron branches in the muscle to make contact with many muscle fibres (dozens to hundreds)
Skeletal muscle only contracts under the control of the nervous system which helps it be a voluntary contraction and this control is initiated at the NMJ.
Explain how an action potential gets to the muscle fibre…
Muscle contraction triggered by action potentials which travel from the brain own the spinal cord in motor neuron. The motor neuron will then extend out of the spinal cord and to the NMJ, generating an action potential in the muscle fibre.
Where is the NMJ usually located?
The NMJ is normally in the middle third of the fibre’s length, so the wave of depolarisation (action potential) spreads over the sarcolemma away from the NMJ in both direction
How acetyl choline released and what does it do?
The action potential invades the motor nerve terminal at the NMJ. The NMJ is a chemical synapse, so depolarisation at the nerve terminal results in the release of a neurotransmitter known as Acetyl Choline. Therefore the NMJ is said to be a cholinergic synapse. Acetyl choline acts as receptors on the muscle fibre’s post synaptic surface to initiate an action potential in the muscle fibre.
ACh is what allows the transmission of a nerve impulse to then initiate excitation-contraction coupling so then we initiate contraction of the muscle (generate force). ACh does this by changing the permeability of the sarcolemma to sodium. The sodium levels in the ECF are high so to change the permeability means that the sodium will want to flow with the concentration gradient and therefore rush across the sarcolemma. This will therefore mean that more positive charges are going into a negative environment which will raise the membrane potential which is depolarisation.
NMJ is said to be a ….
Cholinergic synapse - this is because it releases ACh across the synaptic cleft which will bind to receptors on the muscle (Definition of Cholinergic - stimulated by or releasing acetylcholine or a related compound.)
Synaptic bulb and synaptic cleft and their relation to neurotransmitters …
The end bulb contains synaptic vesicles which are filled with a neurotransmitter substance. When a nerve impulse travels down the axon and reaches the end bulb the neurotransmitter is released into a small space, the synaptic cleft.
Chemical synaptic transmission - describe the image
1 - Action potential triggers the opening of voltage-gated calcium channels
2- a) Calcium ions diffuse into the axon terminal, and b) trigger synaptic vesicles to release ACh by exocytosis
3- ACh diffuses across synaptic cleft, binds to ACh-gated sodium ion channels, and produces a graded depolarisation (Going to come out and basically depolarise the sarcolemma membrane and allow action potential to propagate along that membrane as well)
4- Depolarisation ends as ACh is broken down into acetate and choline by AChE (acetylcholinesterase allows the break down of ACh.)
5- The axon terminal reabsorbs choline from the synaptic cleft and uses it to synthesise new molecules of ACh
What happens as the action potential passes along the membrane?
Recall that muscle fibres have a network of tubular membranes (T-tubules) that are continuous with the sarcolemma. As the action potential passes along the membrane, the depolarisation passes down the T-tubule and is conducted via the T-tubular network into the core of the fibre. As the action potential reaches a triad, the T-tubule-SR junction opens the Ca channels in nearby SR membrane. Calcium diffused through the open calcium channels from a region of very high calcium concentration (inside the SR) to a region of very low calcium concentration (the muscle fibre cytoplasm know as the sarcoplasm)
What role does calcium play in excitation-contraction coupling?
An action potential is going to come along the sarcolemma because it is an excitable membrane. It is travelling away from the NMJ and then goes down the transverse tubule. It is going to interact with the voltage sensors that are sitting in the transverse tubule space and this interacts with the terminal cisternae of the SR and on the terminal cisternae where it is close to the transverse tubule, there is a calcium release channels so the stimulation of the depolarisation from the change in sodium from the ACh is going to change the voltage sensors, it is going to interact with the calcium release channels in the terminal cisternae of the SR and calcium us going to flow out of the SR and that calcium is what is going to initiate contraction of the myofilaments (the thick and thin filaments). This process is what is known as excitation-contraction coupling.
Excitation-contraction overview
The action potential from the nerve causes synaptic transmission at the NMJ to trigger an action potential in the muscle fibre. The muscle action potential spreads over the surface of the sarcolemma and invades the T-tubular system. Depolarisation with the T-tubular system triggers release of calcium from the nearby terminals of the SR. Calcium releases into the sarcoplasm and promotes the binding of calcium to a subunit of the troponin molecule (troponin C). The binding of calcium to troponin causes a change in the shape of troponin which exposes an actin binding site. Myosin then binds actin and changes shape. Force is then generated.
The sequence of events that converts action potentials in a muscle fibre to a contraction is known as excitation-contraction coupling.
There is a direct link (i.e. a coupling) between an action potential in the motor nerve and muscle fibre (“excitation”) and the development of tension by the actin-myosin interaction (“contraction”)
Excitation part of excitation-contraction coupling
Muscle cell becomes depolarised from neurosynaptic transmission at the NMJ. The action potential spreads over the sarcolemma and down to the T-tubules. As it reaches the triad, the depolarisation in the membrane causes the calcium channels in the SR to open. Once the channels open, the calcium diffuses from the SR into the sarcoplasm.
Contraction part of excitation-contraction coupling
Cross bridges between the actin and myosin filaments form, leading to the shortening of the sarcomere and contraction of the muscle cell (and development of tension in muscle)
At rest, the myosin heads are extended, with ADP and Pi bound. Calcium (in the sarcoplasm) binds to troponin causing a conformational shape change that moves tropomyosin from the myosin binding sites on actin. Because the tropomyosin has been moved out of the way, the myosin heads can bind to binding sites on actin forming cross bridges and ADP and Pi are released causing the myosin head to flex = power stroke. As the myosin heads flex, the ends of the sarcomere get dragged closer together. Once the power stroke occurs, ATP binds to the myosin heads, lowering its binding affinity for actin and the cross bridges are broken. Myosin ATPase hydrolyses ATP to ADP and Pi, resetting for another cycle (the myosin head extends again.) Contraction is terminated when calcium is pumped back into the SR with the use of ATP.
What is cross-bridge cycling?
The contraction of a skeletal muscle generates the force necessary to move the skeleton. A contraction is triggered by a series of molecular events known as the cross bridge cycle. In a skeletal muscle fibre, the functional unit of contraction is known as the sarcomere. A sarcomere shortens when myosin heads form cross bridges with actin molecules. The formation of a cross bridge is initiated when calcium ions, released from the SR, bind to troponin. This binding causes troponin to change shape. Tropomyosin moves away from the myosin binding sites on actin, allowing the myosin heads to bind to actin, and form a cross bridge. Also note that the myosin head must be activated before a cross bridge cycle can begin. This occurs when ATP binds to the myosin head and is hydrolysed to ADP and inorganic phosphate. The energy liberated from the hydrolysis of ATP activates the myosin head, forcing it into the cocked position. A cross bridge cycle may be divided into four steps….
Step 1 - Cross bridge formation. The activated myosin head binds to actin forming a cross bridge. Inorganic phosphate is released and the bond between myosin and actin become stronger.
Step 2 - The power stroke. ADP is released and the activated myosin head pivots, sliding the thin myofilament toward the centre of the sarcomere.
The power stroke occurs when myosin changes its shape, pulling the thin filaments towards the middle of the sarcomere - that’s what causes sarcomere shortening in muscular contraction.
Step 3 - Cross bridge detachment. When another ATP binds to the myosin head, the link between the myosin head and actin weakens, and the myosin head detaches.
Step 4 - Reactivation of the myosin head. ATP is hydrolysed to ADP and inorganic phosphate. The energy released during hydrolysis reactivates the myosin head returning it to the cocked position.
As long as the binding sites in actin remain exposed, the cross bridge cycle will repeat.Cross bridge cycling ends when calcium ions are actively transported back into the SR. Troponin returns to its original shape, allowing tropomyosin to glide over and cover the myosin binding site on actin.
Power stroke
The power stroke occurs when ADP and phosphate dissociate from the actin active site.
The power stroke occurs when myosin changes its shape, pulling the thin filaments towards the middle of the sarcomere - that’s what causes sarcomere shortening in muscular contraction.
The power stroke occurs when myosin heads flex whilst bound to actin filaments (i.e. whilst cross bridges are formed)
Twitch
A single action potential will result in the release of a pulse of calcium into the sarcoplasm, and short period of tension development will ensue. A bride contraction resulting from such an event is called a twitch.
Tetanus
Many action potentials in rapid sequence results in a sustained release of calcium from the SR, a sustained period of actin-myosin interaction, and a sustained period of contraction. The contraction resulting from such activity is called a tetanus.
What are the factors that determine the amount of force delivered when a muscle is activated?
The amount of force produced by each fibre
The number of fibres activated
The more cross bridges you have the more…
Force that is produced (roughly)
Name a determinant of the number of cross bridges that can form….
Sarcomere’s length
Describe the length-tension curve
The amount of force a sarcomere can produce a maximal when overlap between thick (myosin) and thin (actin) filaments is optimal. As the sarcomere lengthens, overlap between actin and myosin is reduced, so the number of cross bridges is reduces and forces therefore almost falls to zero when there is no actin-myosin overlap. Force also declines as myofilaments overlap increases because the thin actin filaments overlap in the centre of the sarcomere and interfere with optimal cross bridge formation. This means that each muscle has an optimal length where it will be strongest, and when either longer or shorter than that length, it will be weaker.
Less overlap of actin and myosin = reduced number of cross bridges = reduced force
Too much overlap = no where for the filaments to move = reduced force
What is rate coding and summation?
Rate coding - an increase in force is proportional to the frequency of action potentials (more action potentials per second means an increase in force. Lower frequency of action potentials means less force.) Summation occurs as successive stimuli are added together to produce a stronger muscle contraction. (gradual increase in force)
Describe recruitment and its role in the amount of force created
We can activate more motor units and therefore generate more force in a process called recruitment.
The amount of force a whole muscle can produce is a function of the force produced by each fibre, AND of the number of fibres activated. The number of fibres activated is regulated by how many neurons are active at one time. A small number of active neurons tends to produce low force from the muscle, with the amount of force generally increasing as more motor units are activated. This process of activating more motor units to make more force is called recruitment.
Action potential
A self propagating electrical impulse that occurs in excitable tissues that is characterised by a transient reversal in membrane potential.
Order myo words from smallest to largest …
myofilaments, myofibrils, myofibre
Way to remember is that as the myo name gets larger, the structure gets smaller
Put these in the correct order - actin and myosin filaments, muscle fibres, fascicles, myofibrils and muscle
Muscle - fascicles - muscle fibres (cells) - myofibrils - actin and myosin filaments
Myotendinous junction
Where the muscle attaches to tendon
Osteoteninous junction
Where the tendon attaches to bone
Thinking about the microscopic structure of muscle, why does a muscle create the greatest tension in the middle of the range of movement?
Optimal overlap between actin and myosin myofilaments
