Summary

This document reviews skeletal muscle function, structure, motor units and neuromuscular transmission. It covers topics like sarcomeres, myofibrils, and the properties of muscle cells.

Full Transcript

Skeletal Muscle Function **Skeletal muscle structure** A single skeletal muscle contains many muscle fibers. Different components of the skeletal muscle are surrounded by layers of connective tissue: the endomysium, perimysium, and epimysium. - Each individual muscle fiber is surrounded by a de...

Skeletal Muscle Function **Skeletal muscle structure** A single skeletal muscle contains many muscle fibers. Different components of the skeletal muscle are surrounded by layers of connective tissue: the endomysium, perimysium, and epimysium. - Each individual muscle fiber is surrounded by a delicate layer of connective tissue called endomysium. - Muscle fibers are grouped into bundles called fascicles. Each fascicle is surrounded by perimysium. - An entire muscle is surrounded by epimysium. Each skeletal muscle fiber is long (up to 30 cm; 12 inches) and striated in appearance. The striations in skeletal muscle are a result of many repeating units called **sarcomeres**, which are the functional units of the muscle. Sarcomeres are found in myofibrils. A diagram of a muscle Description automatically generated **Skeletal muscle structure** The properties of each muscle cell facilitate its functions. - **Contractile:** It has the ability to shorten in response to adequate electrical stimulation. - **Elastic:** It has the ability to recoil and regain the resting length after being stretched. - **Excitable:** It has the ability to receive and respond to a stimulus. - **Extensible:** It has the ability to stretch when not contracted. **Motor units** Muscles contract in response to electrical stimulation (that is, action potentials). Groups of muscle fibers within a muscle are innervated by motor neurons; one motor neuron and all the muscle fibers that it innervates is collectively referred to as a **motor unit**. An action potential in a single* *motor neuron will cause subsequent activation and contraction of all* *of the muscle fibers innervated by that motor neuron. Motor units vary greatly in size. A single motor neuron may innervate only a few muscle fibers (small motor unit), or thousands of muscle fibers (large motor unit). A single muscle will often contain motor units of varying sizes, and several motor units may work together to coordinate the movement of a single muscle. **Neuromuscular transmission** The motor neuron (of the motor unit) and the muscle fibers that it innervates are separated by a space called the synaptic cleft. Signals from the motor neuron must be transferred across this space to muscle fibers, to elicit a response in the muscle.  The specialized synapse between the motor neuron (of the motor unit) and muscle fiber is called the neuromuscular junction* *(NMJ). Specifically, the NMJ is made up of the axon terminal, synaptic cleft, and motor endplate of the muscle fiber. ![An illustration of a neuromuscular junction. The end of the neuron at the junction is labeled "Axon terminal". The muscle below the junction has thick dark pink bands and thin white bands labeled "contractile proteins". Near the tip of the junction is a small invagination of the muscle labeled "T-tubule". There are blue structures on either side of the t-tubule labeled "Sarcoplasmic reticulum". The junction between the neuron and muscle is magnified. There is a green oval labeled "Mitochondrion" and multiple small circles labeled "Synaptic vesicle" in the presynaptic terminal. The muscle which the axon interacts with is labeled the "Motor endplate". The space between the motor endplate and the presynaptic terminal is labeled the "Synaptic cleft".](media/image2.png) **Muscle fibers and myofibrils** Muscle fibers are surrounded by a sarcolemma (muscle membrane). At regular points along the muscle fiber, the sarcolemma extends deep into the center of the fiber to form structures called t-tubules. Local depolarization of the motor endplate initiates an action potential that travels along the sarcolemma and down t-tubules. An illustration of a neuromuscular junction. The axon of the neuron is wrapped in a purple bubble labeled "Myelin". The end of the neuron at the junction is labeled "Axon terminal" and the surface of the muscle it interacts with is labeled "Postsynaptic membrane". The muscle below the junction has thick dark pink bands labeled "contractile proteins". Near the tip of the junction is a small invagination of the muscle labeled "T-tubule". There are blue structures on either side of the t-tubule labeled "Sarcoplasmic reticulum". **Sarcomeres** Sarcomeres are joined together at their ends by structures called Z lines, to which actin (thin filaments) and myosin (thick filaments) are tethered. Myosin overlaps with actin within the sarcomere. ![An illustration of the structure inside a skeletal muscle fiber. The striated muscle fiber is cut to show the arrangement of myofibrils inside. A myofibril extends from the cross-section and is magnified. The magnified myofibril is made up of a repeating blue, zig-zag-like pattern that represents the Z lines, and a red T-shaped pattern wrapping around the structure that is also repeated and represents the myosin. A sarcomere is magnified from the myofibril to show the arrangement of myosin and actin between Z lines. A sarcomere spans from one Z line to the next. Each Z line is where the blue actin filaments anchor. The red myosin filaments anchored in between the Z lines intercalate with the actin filaments.](media/image4.png) **Recruitment** The process of progressive activation of motor units is called \"recruitment\". The contraction of a whole muscle may require that hundreds of motor axons fire. Motor units are recruited at different stimulus strengths, based on their size. That is, smaller motor units are recruited at lesser stimulus strengths and larger motor units are recruited at greater stimulus strengths. As more motor units are recruited, the strength of muscle contraction increases. You can examine this through electrical stimulation of the peripheral nerve. - At low stimulus strengths, no motor nerves are depolarized and no muscle contraction is seen. - As stimulus strength is increased, some motor neurons are brought above their threshold potential and an action potential is fired. This results in contraction of all the muscle fibers in that motor unit, which causes a twitch (one complete cycle of contraction and relaxation) in the muscle. The force of the twitch increases progressively as more motor nerve fibers are excited. This occurs until a maximum response is reached when all of the motor units that supply the muscle have been activated. **Frequency** Frequency refers to the number of action potentials delivered to a muscle within a set period of time. At low stimulation frequencies, the tension developed in the muscle decreases back to a resting level in between stimulations. Remember that Ca^2+^ is released with each stimulation. The muscle relaxes when nerve stimulation to the muscle stops, and Ca^2+^ is pumped back into the sarcoplasmic reticulum (cleared from the sarcoplasm). Note the relative time difference for an action potential to occur, for Ca^2+^ to be released and taken up again, and for twitch duration. An action potential lasts only a few milliseconds (ms) and is essentially over before Ca^2+^ has been released and the muscle starts to contract. Therefore, it is possible to generate many action potentials during a muscle contraction. If many action potentials are fired in quick succession (that is, the frequency of stimulation is increased), the level of Ca^2+^ that is released into the sarcoplasm will rise, and more Ca^2+^ will be available for crossbridge formation. In this way, by increasing frequency, we can increase the strength and duration of muscle contraction. ** ** **Twitch, summation, and tetanus** A twitch is one complete cycle of contraction and relaxation in a muscle.  A muscle action potential lasts only a few milliseconds. In contrast, the time in which Ca^2+^ remains in the sarcoplasm and the muscle maintains tension lasts much longer. Therefore, it is possible to generate many action potentials while a muscle contracts. Twitch force can be increased by recruiting more motor units to fire simultaneously. This additive effect of muscle stimulation is called summation. Twitch force can also be increased by increasing the **frequency** of action potentials in motor axons. Tetanus is a state of sustained maximal muscle contraction. At high stimulation frequencies, the muscle has no time to relax between successive stimuli. The result is a smooth contraction that is much stronger than a single twitch: a **tetanic contraction**. The muscle is now said to be in a state of \"tetanus\". **Incomplete tetanus** (also called \"unfused tetanus\") occurs if stimulation frequency is high, but at a rate that still allows partial relaxation of muscle between twitches. **\ Types of contractions** Contraction refers to the generation of tension within muscle fibers that results from excitation of motor neurons. Muscle fibers are able to lengthen, shorten, or remain the same length as they generate tension during a contraction. Skeletal muscle contractions are often described as being **isotonic** or **isometric**. Isotonic contractions can be further described as concentric or eccentric. +-----------------+-----------------+-----------------+-----------------+ | **Type of | **Tension** | **Muscle | **Joint** | | Contraction** | | Length** | | +=================+=================+=================+=================+ | **Isometric** | Muscle develops | Muscle stays | Joint remains | | | tension | the same length | in a fixed | | | | during | position | | | | contraction | (without | | | | | movement) | +-----------------+-----------------+-----------------+-----------------+ | **Isotonic\ | Muscle tension | Muscle shortens | Contraction | | \ | stays the same | | results in | | - Concentric** | | Muscle | movement at the | | |   | lengthens | joints that the | | **- Eccentric** | | | muscle affects | +-----------------+-----------------+-----------------+-----------------+ **~Examples~** **Isotonic contraction** - Hold a heavy book in your hand with your arm straight out and palm turned upwards. - While still holding the book, do a slow biceps curl up to your shoulder. In this situation, the biceps brachii muscle contracts concentrically to lift the weight. At the same time, the triceps brachii contracts eccentrically to help control this lifting movement. ** ** **Isometric contraction** - Hold something heavy in your hands (like a book or a laptop). - Extend your arms straight out in front of you and hold this position.  To overcome gravity, the muscles have to contract to maintain that position but muscle length is unchanged.  Muscle and EMG Skeletal muscles support our bones and do the work for locomotion. Each muscle is made up of individual muscle fibers arranged in bundles called fascicles.  **Skeletal muscle structure** Groups of muscle fibers within a muscle are innervated by motor neurons; one motor neuron and all the muscle fibers that it innervates is collectively referred to as a **motor unit**. An action potential in a single* *motor neuron will cause subsequent activation and contraction of all* *of the muscle fibers innervated by that motor neuron. Motor units vary greatly in size. A single motor neuron may innervate only a few muscle fibers (small motor unit), or thousands of muscle fibers (large motor unit). A single muscle will often contain motor units of varying sizes, and these motor units work together to coordinate the movement of a single muscle. **Muscle fatigue** **Muscle fatigue** is the inability to maintain force during muscle contraction. Specifically, repeated stimulation of a skeletal muscle fiber will eventually lead to a decrease in tension in that fiber, even if stimulation remains the same. It\'s important to recognize the difference between muscle fatigue and muscle damage. In both cases, the muscle is unable to maintain the desired force. However, muscle fatigue is reversible with a short period of rest. In contrast, the force of muscle contraction may be compromised for days if muscles are damaged. The causes of muscle fatigue are not well understood, and specific sites involved in fatigue are difficult to define due to the complexity of the central nervous system (CNS). Psychological causes include the following: - Loss of \"central drive\" or motivation to complete a physical task. - Changes in the sense of effort (the perceived psychological effort) to complete a physical task. **Why understanding muscle anatomy and fatigue is important clinically** Skeletal muscle cells make up about 70% of the cell mass of the body. Normally, functioning skeletal muscle is essential for all movements. Although disease of muscle itself is rare and mostly inherited (the muscular dystrophies), trauma to muscle is very common. You will commonly see patients with loss of muscle function as a consequence of strokes damaging neurons in the brain. Loss of muscle function can also occur in peripheral nerve disease, and when neuromuscular transmission is compromised. Managing patients with muscular disease requires skill and knowledge. **Neuromuscular transmission** The motor neuron (of the motor unit) and the muscle fibers that it innervates are separated by a space called the synaptic cleft. Signals from the motor neuron must be transferred across this space to muscle fibers, to elicit a response in the muscle.  The specialized synapse between the motor neuron (of the motor unit) and muscle fiber is called the neuromuscular junction* *(NMJ). Specifically, the NMJ is made up of the axon terminal, synaptic cleft, and motor endplate of the muscle fiber. A labeled illustration of a neuromuscular junction. The end of the neuron at the junction is labeled "Axon terminal". The muscle below the junction has thick dark pink bands and thin white bands labeled "contractile machinery". Near the tip of the junction is a small invagination of the muscle labeled "T-tubule". There are blue structures on either side of the t-tubule labeled "Sarcoplasmic reticulum". The junction between the neuron and muscle is magnified. There is a green oval labeled "Mitochondrion" and multiple small circles labeled "Synaptic vesicle" in the presynaptic terminal. The muscle which the axon interacts with is labeled the "Motor endplate". The space between the motor endplate and the presynaptic terminal is labeled the "Synaptic cleft". **1** **2** **3** **4** **~Calcium\ entry\ into\ axon\ terminal~** The arrival of an action potential in the axon terminal of the motor neuron opens voltage-sensitive calcium ion (Ca^2+^) channels. This allows Ca^2+ ^ions to enter the neuron. ![An image of the neuromuscular junction with a circle highlighting a section of the membrane of the presynaptic terminal. The circle is near the axon and is not in the synaptic cleft.](media/image5.png) An image with 2 illustrations of a labeled calcium channel in a membrane. In the first illustration, there are labeled calcium ions on one side of the membrane. The channel is closed and the membrane is blue. In the second illustration, the membrane has a yellow gradient and is labeled "Action potential". The channel is open, and calcium ions are on both sides of the membrane. ![An image of the neuromuscular junction with a circle highlighting a section of the membrane of the presynaptic terminal. The circle is in the synaptic cleft.](media/image7.png) A labeled illustration of acetylcholine (ACh) in the axon terminal and the synaptic cleft. The ACh is stored in synaptic vesicles in the axon terminal. A vesicle has merged with the membrane of the axon terminal and ACh molecules are in the synaptic cleft. ![An image of the neuromuscular junction with a circle highlighting a section of the membrane of the motor endplate.](media/image9.png) An image of 2 illustrations of a labeled nicotinic acetylcholine receptor (nAChR) across a membrane between the synaptic cleft and the motor endplate. In the first illustration, there are labeled sodium ions in the synaptic cleft and an acetylcholine (ACh) molecule is in the nAChR. The nAChR is closed. In the second illustration, there are sodium ions in both the synaptic cleft and the motor endplate and two ACh molecules in the nAChR. The nAChR is open. ![An image of the neuromuscular junction with a circle highlighting a section of the membrane of the motor endplate.](media/image9.png) An image of 2 illustrations of an open nicotinic acetylcholine receptor (nAChR) across a membrane with sodium ions on both sides. In the first illustration, the membrane is colored red, and there is an ion at one end of the channel with an arrow pointing toward the other end. In the second illustration, the membrane has a yellow gradient and the ion is halfway through the channel. **Electromyography ** Electromyography is a technique that measures the electrical activity of skeletal muscles at rest and during contraction. The device used is an electromyograph and the data recorded is an electromyogram (EMG). An EMG can be analyzed in terms of the **timing **of contraction and relaxation, **pattern** of motor unit recruitment, and **amplitude** which reflects the strength or force of contraction. An EMG can be recorded using two methods: 1. Surface EMG; electrodes are placed on the skin surface. 2. Intramuscular EMG; needle electrodes are inserted into the muscle through the skin. ![A demonstration of electrode attachment on the arm. There is a grey wristband and 4 electrodes colored red, maroon, black, and white. The red and maroon electrodes are placed on the posterior surface of the arm, maroon higher than red. The black and white electrodes are placed on the anterior surface of the arm, black higher than the white. Each electrode has a corresponding color lead which attaches to the bio amp. The grey wristband on the wrist has a green lead which attaches to the bio amp. The bio amp is connected to the PowerLab.](media/image12.png) **Surface EMG** A demonstration of electrode attachment on the arm. There is a grey wristband and 4 leads colored red, brown, black, and white. The red and brown leads are placed in the posterior muscles of the arm, the brown closer to the shoulder than the red. The black and white leads are placed in the anterior muscles of the arm, the black closer to the shoulder than the white. Each lead attaches to the bio amp. The grey wristband on the wrist has a green lead that attaches to the bio amp. The bio amp is connected to the PowerLab. **Intramuscular EMG** The size and shape of the waveform measured provide information about the ability of the muscle to respond when the nerves are stimulated. In the clinical setting, EMG is most often used when people have symptoms of weakness and the examination shows impaired muscle strength. It can help to differentiate muscle weakness caused by neurological disorders from other conditions.  The EMG provides a depiction of the timing and pattern of muscle activity during complex movements. The raw surface EMG signal reflects the electrical activity of the muscle fibers active at that time. Motor units fire asynchronously. With exceedingly weak contractions, there may be very few motor units activated or \"firing\". This means that only a single motor unit is firing at any time. So it is possible that the activity of a single motor unit can be seen in an EMG. As the strength of the muscular contraction increases, the density of action potentials increase and the raw signal at any time may represent the electrical activity of perhaps thousands of individual fibers. The raw EMG signal may be processed to calculate the intensity of EMG activity. ![A chart with 2 channels over time, the upper depicting biceps in millivolts and the lower depicting triceps in millivolts, with 2 sections, the first unnamed and the second "Tricep contraction". In the first section, the bicep signal has activity between 0.3 and negative 0.3 millivolts while the tricep signal has activity between 0.05 and negative 0.05 millivolts. In the second section, the bicep signal has activity between 0.01 and negative 0.01 millivolts while the tricep signal has activity between 0.2 and negative 0.2 millivolts.](media/image14.png) **The raw EMG signal during voluntary contractions of antagonistic muscles, the biceps (green) and triceps (pink).** **Coactivation** **Coactivation** is a phenomenon in which the contraction of an agonist muscle leads to minor activity in the antagonist muscle. The physiological significance of this is not entirely clear, but it has been suggested that it helps stabilize the joint during isotonic contractions. **Skeletal muscle contractions** Contraction refers to the generation of tension within muscle fibers that results from excitation of motor neurons. Muscle fibers are able to lengthen, shorten, or remain the same length as they generate tension during a contraction. Skeletal muscle contractions are often described as being **isotonic** or **isometric**. Isotonic contractions can be further described as concentric or eccentric. +-----------------+-----------------+-----------------+-----------------+ | **Type of | **Tension** | **Muscle | **Joint** | | Contraction** | | Length** | | +=================+=================+=================+=================+ | **Isometric** | Muscle develops | Muscle stays | Joint remains | | | tension | the same length | in a fixed | | | | during | position | | | | contraction | (without | | | | | movement) | +-----------------+-----------------+-----------------+-----------------+ | **Isotonic\ | Muscle tension | Muscle shortens | Contraction | | \ | stays the same | | results in | | - Concentric** | | Muscle | movement at the | | |   | lengthens | joints that the | | **- Eccentric** | | | muscle affects | +-----------------+-----------------+-----------------+-----------------+ **Evoked EMG** Evoked EMGs are produced by electrical stimulation of a motor nerve supplying a muscle. For example, electrical stimulation of the median nerve at the wrist results in contraction of the abductor pollicis brevis muscle which causes the thumb to twitch. The motor nerve to the abductor pollicis brevis muscle (the median nerve) is easy to stimulate at the wrist and elbow. Brief electrical pulses are administered through the skin to the nerve, and the time it takes for the muscle to contract in response to the electrical pulse is recorded. The speed of the response is dependent on the conduction velocity. In general, the range of normal conduction velocities will be approximately 40--60 meters per second. However, the normal conduction velocity may vary from one individual to another and from one nerve to another. An illustration of the muscles and nerves in the arm. Labeled are the "Abductor pollicis brevis" muscle and the "Median nerve". The abductor pollicis spans from the wrist to the base of the thumb. The median nerve runs along the inner arm muscles, across the inside of the elbow, down the inner side of the forearm to the wrist. **Some muscles of the forearm and hand.** In a clinical setting, EMG and nerve conduction studies are usually done together. Nerve and muscle disorders cause the muscles to react in abnormal ways. Measuring the electrical activity in muscles and nerves can help to detect the presence, location, and extent of diseases. Examples are listed below: - Diseases that damage muscle tissue (for example, muscular dystrophy).  - Diseases that damage nerves (for example, amyotrophic lateral sclerosis or \"Lou Gehrig\'s disease\"). - Nerve injury, where the actual site of nerve damage can often be located.  **Muscle fatigue ** Skeletal muscle needs a steady supply of ATP in order to contract. When ATP production fails to keep pace with ATP usage, muscle fatigue begins and muscle activity is reduced even though the stimulation to the muscle may continue. ATP can be generated through aerobic respiration (requires oxygen, O~2~) and anaerobic respiration (does not require O~2~). Glycolysis is one of the main processes involved in cellular respiration. It involves the breakdown of glucose into pyruvate, which is then processed to produce ATP. These two processes are explained in more detail below. - **Aerobic glycolysis**: If O~2~ supplies are sufficient, pyruvate enters the Krebs cycle in the mitochondria and is broken down into carbon dioxide (CO~2~) and water (H~2~O). This generates large amounts of ATP. - **Anaerobic glycolysis**: If O~2~ supplies are insufficient, pyruvate cannot enter the Krebs cycle and is instead converted to lactate (lactic acid). This makes a much smaller amount of ATP. **Aerobic and anaerobic mechanisms of ATP production.** Some muscle fibers are more resistant to fatigue than others. They may have more mitochondria and hence a greater capacity for oxidative metabolism, or they may have greater stores of phosphocreatine. However, in animals and humans fatigue occurs primarily because the motor drive from the brain (or the \"central drive\") is reduced, rather than as a result of depletion of the muscle energy reserves. The role of the \"central drive\" also explains why, some people can show \"super-human\" strength for brief periods in extreme situations. Fatigue is not well understood. Factors that have been proposed to explain the fall in force during prolonged contraction include the following: - Changes in the \"sense of effort\". - Loss of the \"central drive\". - Failure of the action potential to reach the skeletal muscle. - Impaired initiation or conduction of action potentials along the muscle. - Impaired release or reuptake of Ca^2+^ for crossbridge formation. - Depletion of energy sources in crossbridge formation. - Metabolic changes in the muscle cell (such as a build-up of protons which can make the skeletal muscle acidic, inhibiting any further anaerobic glycolysis). - Reduction in muscle blood flow owing to compression of blood vessels.

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