after nervous stimulation stops what prevents ach in the synaptic cleft from continuing to stimulate

Neuromuscular Junctions

Skeletal muscle cell contraction occurs afterward a release of calcium ions from internal stores, which is initiated by a neural signal. Each skeletal muscle cobweb is controlled by a motor neuron, which conducts signals from the brain or spinal cord to the musculus.

The post-obit list presents an overview of the sequence of events involved in the contraction bike of skeletal muscle:

1. The action potential travels down the neuron to the presynaptic axon terminal.
2. Voltage-dependent calcium channels open up and Ca²⁺ ions flow from the extracellular fluid into the presynaptic neuron's cytosol.
3. The influx of Ca²⁺ causes neurotransmitter (acetylcholine)-containing vesicles to dock and fuse to the presynaptic neuron's jail cell membrane.
4. Vesicle membrane fusion with the nerve jail cell membrane results in the emptying of the neurotransmitter into the synaptic cleft; this process is chosen exocytosis.
5. Acetylcholine diffuses into the synaptic fissure and binds to the nicotinic acetylcholine receptors in the motor cease-plate.
6. The nicotinic acetylcholine receptors are ligand-gated cation channels, and open when bound to acetylcholine.
7. The receptors open, assuasive sodium ions to menstruation into the muscle'southward cytosol.
8. The electrochemical gradient across the muscle plasma membrane causes a local depolarization of the motor terminate-plate.
9. The receptors open, allowing sodium ions to flow into and potassium ions to flow out of the muscle's cytosol.
10. The electrochemical gradient beyond the muscle plasma membrane (more than sodium moves in than potassium out) causes a local depolarization of the motor end-plate.
11. This depolarization initiates an activeness potential on the musculus cobweb cell membrane (sarcolemma) that travels across the surface of the muscle cobweb.
12. The action potentials travel from the surface of the muscle jail cell along the membrane of T tubules that penetrate into the cytosol of the prison cell.
13. Action potentials along the T tubules cause voltage-dependent calcium release channels in the sarcoplasmic reticulum to open, and release Ca²⁺ ions from their storage identify in the cisternae.
14. Ca²⁺ ions diffuse through the cytoplasm where they demark to troponin, ultimately allowing myosin to interact with actin in the sarcomere; this sequence of events is called excitation-contraction coupling.
15. Every bit long equally ATP and another nutrients are available, the mechanical events of contraction occur.
16. Meanwhile, dorsum at the neuromuscular junction, acetylcholine has moved off of the acetylcholine receptor and is degraded by the enzyme acetylcholinesterase (into choline and acetate groups), causing termination of the betoken.
17. The choline is recycled back into the presynaptic final, where it is used to synthesize new acetylcholine molecules.

Anatomy and Physiology of the Neuromuscular Junction

Anatomy

We stimulate skeletal muscle contraction voluntarily. Electrical signals from the brain through the spinal cord travel through the axon of the motor neuron. The axon then branches through the muscle and connects to the private muscle fibers at the neuromuscular junction. The folded sarcolemma of the muscle fiber that interacts with the neuron is called the motor finish-plate; the folded sarcolemma increases surface expanse contact with receptors. The ends of the branches of the axon are called the synaptic terminals, and exercise non actually contact the motor stop-plate. A synaptic cleft separates the synaptic terminal from the motor end-plate, but merely past a few nanometers.

Communication occurs between a neuron and a muscle fiber through neurotransmitters. Neural excitation causes the release of neurotransmitters from the synaptic terminal into the synaptic cleft, where they tin then bind to the appropriate receptors on the motor end-plate. The motor end-plate has folds in the sarcolemma, chosen junctional folds, that create a large surface surface area for the neurotransmitter to bind to receptors. Generally, there are many folds and invaginations that increase surface surface area including junctional folds at the motor endplate and the T-tubules throughout the cells.

Physiology

The neurotransmitter acetylcholine is released when an action potential travels down the axon of the motor neuron, resulting in altered permeability of the synaptic concluding and an influx of calcium into the neuron. The calcium influx triggers synaptic vesicles, which package neurotransmitters, to demark to the presynaptic membrane and to release acetylcholine into the synaptic cleft by exocytosis.

Review the section of this course nearly membranes if you need a refresher.

The balance of ions within and outside a resting membrane creates an electrical potential departure across the membrane. This means that the inside of the sarcolemma has an overall negative charge relative to the exterior of the membrane, which has an overall positive accuse, causing the membrane to exist polarized. Once released from the synaptic terminal, acetylcholine diffuses across the synaptic crevice to the motor stop-plate, where it binds to acetylcholine receptors, primarily the nicotinic acetylcholine receptors. This binding causes activation of ion channels in the motor end-plate, which increases permeability of ions via activation of ion channels: sodium ions flow into the muscle and potassium ions catamenia out. Both sodium and potassium ions contribute to the voltage difference while ion channels control their move into and out of the jail cell. As a neurotransmitter binds, these ion channels open, and Na+ ions enter the membrane. This reduces the voltage deviation betwixt the inside and outside of the prison cell, which is called depolarization. As acetylcholine binds at the motor-end plate, this depolarization is called an end-plate potential. It so spreads along the sarcolemma, creating an activeness potential as voltage-dependent (voltage-gated) sodium channels adjacent to the initial depolarization site open. The activeness potential moves across the entire cell membrane, creating a moving ridge of depolarization.

Afterward depolarization, the membrane needs to be returned to its resting land. This is chosen repolarization, during which sodium channels close and potassium channels open. Because positive potassium ions (K⁺) movement from the intracellular space to the extracellular space, this allows the inside of the prison cell to over again go negatively charged relative to the outside. During repolarization, and for some time after, the prison cell enters a refractory menses, during which the membrane cannot go depolarized again. This is because in order to have another action potential, sodium channels need to return to their resting state, which requires an intermediate pace with a delay.

Propagation of an activity potential and depolarization of the sarcolemma incorporate the excitation portion of excitation-contraction coupling, the connection of electrical action and mechanical contraction. The structures responsible for coupling this excitation to contraction are the T tubules and sarcoplasmic reticulum (SR). The T tubules are extensions of the sarcolemma and thus conduct the action potential along their surface, conducting the moving ridge of depolarization into the interior of the jail cell. T tubules form triads with the ends of ii SR called terminal cisternae. SRs, and especially terminal cisternae, contain high concentrations of Ca²⁺ ions inside. As an action potential travels forth the T tubule, the nearby final cisternae open their voltage-dependent calcium release channels, allowing Ca²⁺ to diffuse into the sarcoplasm. The influx of Caⁱⁱ⁺ increases the amount of calcium available to bind to troponin. Troponin leap to Ca²⁺ undergoes a conformational change that results in tropomyosin moving on the actin filament. When tropomyosin moves, the myosin binding site on the actin is uncovered. This continues as long equally excess Ca²⁺ is available in the sarcoplasm. When there is no more than complimentary Caⁱⁱ⁺ available to bind to troponin, the contraction will stop. To restore Ca²⁺ levels back to a resting state, the excess Caⁱⁱ⁺ is actively transported dorsum into the SR. In a resting state, Ca^two+ is retained inside the SR, keeping sarcoplasmic Ca^two+ levels low. Low sarcoplasmic calcium levels prevent unwanted muscle contraction.

Neurotransmitters

Acetylcholine, ofttimes abbreviated every bit ACh, is a neurotransmitter released by motor neurons that binds to receptors in the motor stop-plate. Information technology is an extremely of import small molecule in human physiology. On the neuron side of the synaptic cleft, there are typically 300,000 vesicles waiting to be exocytosed at any time and each vesicle contains upward to x,000 molecules of acetylcholine.

ACh is produced past the reaction of Acetyl coenzyme A (CoA) with a choline molecule in the neuron cell trunk. After it is packaged, transported, and released, it binds to the acetylcholine receptor on the motor terminate-plate; it is degraded in the synaptic scissure past the enzyme acetylcholinesterase (Anguish) into acetate (and acetic acrid) and choline. The choline is recycled back into the neuron. AChE resides in the synaptic scissure, breaking down ACh so that it does not remain bound to ACh receptors, which would interrupt normal control of muscle contraction. In some cases, insufficient amounts of ACh forestall normal muscle wrinkle and cause muscle weakness.

Botulinum toxin prevents ACh from being released into the synaptic fissure. With no ACh binding to its receptors at the motor cease-plate, no action potential is produced, and muscle wrinkle cannot occur. Botulinum toxin is produced by Clostridium botulinum, a bacterium sometimes found in improperly canned foods. Ingestion of very small amounts tin crusade botulism, which tin cause death due to the paralysis of skeletal muscles, including those required for breathing.

Cellular Musculus Contraction

ATP supplies the energy for muscle wrinkle to take place. In add-on to its direct role in the cross-bridge cycle, ATP besides provides the energy for the active-send Na⁺/K⁺ and Ca^two+ pumps. Muscle wrinkle does not occur without sufficient amounts of ATP. The amount of ATP stored in muscle is very low, only sufficient to power a few seconds worth of contractions. As it is broken down, ATP must therefore be regenerated and replaced quickly to allow for sustained contraction.

Ane ATP moves ane myosin head one step. This can generate three picoNewtons (pN) of isometric force, or motion 11 nanometers. Three pN is a very small strength—a man bite, generated by muscle, can generate 500 trillion pN of force. And 11 nm is a very minor distance— one inch has 25 million nanometers.

There are three mechanisms by which ATP tin be regenerated: creatine phosphate metabolism, anaerobic glycolysis, and aerobic respiration.

Creatine phosphate is a phosphagen, which is a compound that tin store energy in its phosphate bonds. In a resting muscle, backlog ATP (adenosine triphosphate) transfers its energy to creatine, producing ADP (adenosine diphosphate) and creatine phosphate. When the muscle starts to contract and needs energy, creatine phosphate and ADP are converted into ATP and creatine by the enzyme creatine kinase. This reaction occurs very rapidly; thus, phosphagen-derived ATP powers the first few seconds of musculus contraction. However, creatine phosphate can only provide approximately 15 seconds worth of energy, at which point another energy source has to exist available.

Afterward the available ATP from creatine phosphate is depleted, muscles generate ATP using glycolysis. Glycolysis is an anaerobic process that breaks downwardly glucose (carbohydrate) to produce ATP; however, glycolysis cannot generate ATP as chop-chop as creatine phosphate. The sugar used in glycolysis can be provided by blood glucose or past metabolizing glycogen that is stored in the muscle. Each glucose molecule produces ii ATP and two molecules of pyruvate, which tin be used in aerobic respiration or converted to lactic acid.

If oxygen is available, pyruvic acid is used in aerobic respiration. However, if oxygen is non available, pyruvic acrid is converted into lactic acid, which may contribute to muscle fatigue and pain. This occurs during strenuous exercise when high amounts of free energy are needed but oxygen cannot be delivered to muscle at a rate fast enough to encounter the whole demand. Anaerobic glycolysis cannot be sustained for very long (approximately i minute of muscle action), but it is useful in facilitating brusk bursts of high-intensity output. Glycolysis does not employ glucose very efficiently, producing just two ATP molecules per molecule of glucose, and the by-production lactic acid contributes to muscle fatigue as information technology accumulates. Lactic acid is transported out of the muscle into the bloodstream, but if this does not happen quickly plenty, lactic acid can cause cellular pH levels to drop, affecting enzyme action and interfering with muscle contraction.

Aerobic respiration is the breakup of glucose in the presence of oxygen to produce carbon dioxide, water, and ATP. Aerobic respiration in the mitochondria of muscles uses glycogen from musculus stores, blood glucose, pyruvic acid, and fatty acids. Approximately 95 percent of the ATP required for resting or moderately active muscles is provided by aerobic respiration. Aerobic respiration is much more than efficient than anaerobic glycolysis, producing approximately 38 ATP molecules per molecule of glucose. However, aerobic respiration does not synthesize ATP as quickly as anaerobic glycolysis, meaning that the ability output of muscles declines, but lower-power contractions tin can be sustained for longer periods.

Muscles crave a large amount of energy, and thus require a abiding supply of oxygen and nutrients. Blood vessels enter muscle at its surface, after which they are distributed through the entire muscle. Blood vessels and capillaries are plant in the connective tissue that surrounds muscle fascicles and fibers, allowing oxygen and nutrients to be supplied to musculus cells and metabolic waste to be removed. Myoglobin, which binds oxygen similarly to hemoglobin and gives muscle its red color, is institute in the sarcoplasm.This combination of dissimilar energy sources is important for different types of muscle activity. As an illustration, a cup of java with lots of carbohydrate provides a quick burst of energy only not for very long. A counterbalanced repast with complex carbohydrates, protein and fats takes longer to impact usa, but provides sustained energy.

After the first few seconds of exercise, available ATP is used upwards. After the next few minutes, cellular glucose and glycogen are depleted. After the side by side xxx minutes, the body's supply of glucose and glycogen are depleted. After that time, fatty acids and other energy sources are used to brand ATP. That'due south why we should exercise for more than thirty minutes to lose weight (i.east. lose fatty). Sometimes, time is of import.

Sarcomere Wrinkle

You have already learned almost the anatomy of the sarcomere,with its coordinated actin thin filaments and myosin thick filaments. For a muscle cell to contract, the sarcomere must shorten in response to a nerve impulse. The thick and thin filaments practise non shorten, simply they slide past one some other, causing the sarcomere to shorten while the filaments remain the same length. This procedure is known as the sliding filament model of muscle contraction. The machinery of contraction is accomplished by the binding of myosin to actin, resulting in the formation of cross-bridges that generate filament movement.

When a sarcomere shortens, some regions shorten while others remain the same length. A sarcomere is defined as the altitude betwixt ii consecutive Z discs or Z lines. When a musculus contracts, the distance between the Z discs is reduced. The H zone, the central region of the A zone, contains simply thick filaments and shortens during wrinkle. The I band contains only thin filaments and also shortens. The A ring does not shorten; it remains the aforementioned length, but A bands of adjacent sarcomeres move closer together during contraction. Thin filaments are pulled past the thick filaments towards the center of the sarcomere until the Z discs arroyo the thick filaments. The zone of overlap, where thin filaments and thick filaments occupy the aforementioned area, increases as the thin filaments movement in.

The platonic length of a sarcomere to produce maximal tension occurs when all of the thick and thin filaments overlap. If a sarcomere is stretched past this ideal length, some of the myosin heads in the thick filaments are not in contact with the actin in the sparse filaments, and fewer cantankerous-bridges can form. This results in fewer myosin heads pulling on actin, and less tension is produced. If a sarcomere is shortened, the zone of overlap is reduced as the thin filaments reach the H zone, which is composed of myosin tails. Because myosin heads course cross-bridges, actin will not bind to myosin in this zone, again reducing the tension produced by the muscle. If further shortening of the sarcomere occurs, thin filaments begin to overlap with each other, further reducing cross-span germination and the amount of tension produced. If the muscle were stretched to the signal where thick and thin filaments do non overlap at all, no cross-bridges are formed, and no tension is produced. This corporeality of stretching does not commonly occur, as accessory proteins and connective tissue oppose farthermost stretching.

With big numbers of relatively weak molecular motors, we tin can more easily accommodate the force to meet our needs. Otherwise, nosotros would regularly be producing too piddling or too much force for most of our tasks. Also, molecules are only capable of generating small forces based on their molecular construction.

Neural Stimulation of Contraction

You take already learned about how the data from a neuron ultimately leads to a muscle prison cell contraction.

Revisit previous fabric for a review of neuromuscular junctions.

One action potential in a motor neuron produces one contraction. This wrinkle is chosen a twitch. Nosotros think of "muscle twitches" every bit spasms that we tin can't command, but in physiology, a twitch is a technical term describing a muscle response to stimulation. A single twitch does not produce any significant musculus contraction. Multiple activeness potentials (repeated stimulation) are needed to produce a muscle contraction that can produce piece of work.

A twitch can concluding from a few milliseconds up to 100 milliseconds, depending on the muscle blazon. The tension produced by a single twitch can be measured by a myogram, which produces a graph illustrating the amount of tension produced over time. When combined with a plot of electric signaling, the myogram shows three phases that each twitch undergoes. The first menses is the latent period, during which the action potential is being propagated along the membrane and Ca²⁺ ions are released from the sarcoplasmic reticulum (SR). No tension or contraction is produced at this point, merely the atmospheric condition for wrinkle are being established. This is the phase during which excitation and contraction are being coupled but contraction has notwithstanding to occur. The contraction phase occurs later on the latent period when calcium is being used to trigger cross-span formation. This period lasts from the get-go of contraction to the point of peak tension. The last phase is the relaxation phase, when tension decreases as wrinkle stops. Calcium is pumped out of the sarcoplasm, dorsum into the SR, and cross-bridge cycling stops. The muscle returns to a resting land. At that place is a very short refractory period later on the relaxation phase (Review the previous material about the physiology of a neuromuscular junction)

A single twitch does non produce whatsoever significant muscle activity in a living trunk. Normal muscle contraction is more sustained, and it can be modified to produce varying amounts of strength. This is chosen a graded muscle response. The tension produced in a skeletal musculus is a function of both the frequency of neural stimulation and the number of motor neurons involved.

The charge per unit at which a motor neuron delivers action potentials affects the contraction produced in a muscle cell. If a muscle prison cell is stimulated while a previous twitch is still occurring, the second twitch will non have the same forcefulness every bit the first; information technology will be stronger. This effect is called summation, or moving ridge summation, because the furnishings of successive neural stimuli are summed, or added together. This occurs because the second stimulus releases more Ca²⁺ ions, which become available while the muscle is still contracting from the first stimulus (the first moving ridge of calcium ions released). This allows for more cantankerous-bridge germination and greater contraction. Because the 2d stimulus has to go far before the first twitch has completed, the frequency of stimulus determines whether summation occurs or not.

If the frequency of stimulation increases to the bespeak at which each successive stimulus sums with the force generated from the previous stimulus, muscle tension continues to ascent until the tension generated reaches a height point. The tension at this signal is nearly three to four times higher than the tension of a single twitch; this is referred to equally incomplete tetanus. Tetanus is defined as continuous fused contraction. During incomplete tetanus, the muscle goes through quick cycles of contraction with a short relaxation phase. If the stimulus frequency is so loftier that the relaxation phase disappears completely, contractions become continuous in a process called consummate tetanus. This occurs when Ca²⁺ concentrations in the sarcoplasm attain a bespeak at which contractions tin can continue uninterrupted. This contraction continues until the muscle fatigues and can no longer produce tension.

This type of tetanus is not the aforementioned as the disease of the same name that is distinguished by severe sustained contraction of skeletal muscles. The disease, which can be fatal if left untreated, is caused by the bacterium Clostridium tetani, which is present in well-nigh environments. The toxin from the bacterium affects how motor neurons communicate and control muscle contractions, resulting in muscle spasms or sustained contractions, also known as "lockjaw."

Slightly unlike from incomplete tetanus is the phenomenon of treppe. Treppe (from the German term for footstep, referring to stepwise increases in contraction) is a condition in which successive stimuli produce a greater amount of tension, even though tension goes back to the resting state between stimuli (in tetanus, tension does not subtract to the resting state between stimuli). Treppe is similar to tetanus in that the first twitch releases calcium into the sarcoplasm, some of which will non be taken dorsum upwards before the next wrinkle. Each stimulus afterward releases more than calcium, but there is yet some calcium present in the sarcoplasm from the previous stimulus. This extra calcium permits more cross-bridge germination and greater wrinkle with each boosted stimulus up to the bespeak where added calcium cannot be utilized. At this point, successive stimuli will produce a compatible amount of tension.

The strength of contractions is controlled not only by the frequency of stimuli but also by the number of motor units involved in a wrinkle. A motor unit of measurement is defined as a single motor neuron and the respective musculus fibers it controls. Increasing the frequency of neural stimulation can increase the tension produced by a single motor unit, but this tin can only produce a express amount of tension in a skeletal muscle. To produce more tension in an entire skeletal muscle, the number of motor units involved in contraction must exist increased. This procedure is called recruitment.

The size of motor units varies with the sizes of muscle. Small muscles contain smaller motor units and are most useful for fine motor movements. Larger muscles tend to have larger motor units because they are generally non involved in fine control. Fifty-fifty inside a muscle, motor units vary in size. By and large, when a muscle contracts, small motor units will be the first ones recruited in a muscle, with larger motor units added as more force is needed.

All of the motor units in a muscle can be active simultaneously, producing a very powerful contraction. This cannot last for very long because of the energy requirements of muscle wrinkle. To prevent consummate muscle fatigue, typically motor units in a given musculus are not all simultaneously active, just instead, some motor units residuum, while others are active, allowing for longer musculus contractions past the musculus as a whole.

The action potentials produced by pacemaker cells in cardiac muscle are longer than those produced by motor neurons that stimulate skeletal muscle contraction. Thus, cardiac contractions are approximately ten times longer than skeletal muscle contractions. Because of long refractory periods, new activity potential cannot reach a cardiac muscle cell before it has entered the relaxation stage, pregnant that the sustained contractions of tetanus are incommunicable. If tetanus were to occur, the heart would not beat out regularly, interrupting the period of blood through the body.

Skeletal Muscle Tissue and Cobweb Types

Muscle contractions are among the largest free energy-consuming processes in the body, which is non surprising considering the piece of work that muscles constantly practice. Skeletal muscles movement the body in obvious means such as walking and in less noticeable ways such as facilitating respiration. The structure of muscle cells at the microscopic level allows them to convert the chemical energy found in ATP into the mechanical energy of movement. The proteins actin and myosin play large roles in producing this motion.

Skeletal Muscle Anatomy

Remember all of the structures of the fused skeletal muscle cell. If yous need to, review organelles and structures specific to the skeletal muscle cells.

Structures analogous to other cell organelles:

• Sarcolemma—the membrane of the fused skeletal cobweb.
• Sarcoplasm—the cytoplasm of the fused skeletal fiber.
• Sarcoplasmic reticulum—the endoplasmic reticulum of the fused skeletal cobweb.

Specialized structures in muscle cells:

• Transverse tubules (T tubules)—sarcolemma tubes filled with extracellular fluid that coordinate conduction in large musculus cells.
• Terminal cisternae—enlarged sarcoplasmic reticulum structures store calcium and surroundings T tubules.
• Triad—one T tubule and two last cisternae.

Skeletal Musculus Fiber Types

At that place are three master types of skeletal muscle fibers (cells): dull oxidative (SO), which primarily uses aerobic respiration; fast oxidative (FO), which is an intermediate between slow oxidative and fast glycolytic fibers; and fast glycolytic (FG), which primarily uses anaerobic glycolysis. Fibers are defined as slow or fast based on how speedily they contract. The speed of contraction is dependent on how quickly the ATPase of myosin can hydrolyse ATP to produce cantankerous-bridge activity. Fast fibers hydrolyse ATP approximately twice every bit rapidly as slow fibers, resulting in quicker cross-bridge cycling. The master metabolic pathway used determines whether a cobweb is oxidative or glycolytic. If a fiber primarily produces ATP through aerobic pathways, it is oxidative. Glycolytic fibers primarily create ATP through anaerobic glycolysis.

Since And so fibers function for long periods without fatigue, they are used to maintain posture, producing isometric contractions useful for stabilizing bones and joints, and making small movements that happen often but do not crave large amounts of energy. They do not produce high tension, so they are not used for powerful, fast movements that crave loftier amounts of free energy and rapid cross-bridge cycling.

FO fibers are sometimes called intermediate fibers because they possess characteristics that are intermediate between fast fibers and boring fibers. They produce ATP relatively apace, more apace than SO fibers, and thus can produce relatively high amounts of tension. They are oxidative because they produce ATP aerobically, possess high numbers of mitochondria, and practise not fatigue quickly. FO fibers exercise not possess significant myoglobin, giving them a lighter color than the blood-red So fibers. FO fibers are used primarily for movements, such as walking, that crave more free energy than postural control but less energy than an explosive motion such every bit sprinting. FO fibers are useful for this type of movement because they produce more tension than SO fibers and they are more than fatigue-resistant than FG fibers.

FG fibers primarily use anaerobic glycolysis as their ATP source. They have a large bore and possess high amounts of glycogen, which is used in glycolysis to generate ATP apace; thus, they produce high levels of tension. Because they practice not primarily use aerobic metabolism, they do not possess substantial numbers of mitochondria nor large amounts of myoglobin and therefore have a white color. FG fibers are used to produce rapid, forceful contractions to make quick, powerful movements. However, these fibers fatigue quickly, permitting them to only be used for brusque periods.

Most muscles (organs) possess a mixture of each fiber (cell) blazon. The predominant fiber type in a muscle is adamant past the master function of the muscle. Large muscles used for powerful movements incorporate more fast fibers than wearisome fibers. As such, different muscles have different speeds and different abilities to maintain wrinkle over fourth dimension. The proportion of these unlike kinds of muscle fibers will vary among different people and can change within a person with conditioning.

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