Physiological Makeup Essay, Research Paper
PHYSIOLOGY 525SKELETAL MUSCLEJANUARY 28, 1998 There are three types of muscle: skeletal, smooth, and cardiac. From histology you know that skeletal and cardiac muscle are striated and smooth muscle is “smooth”- not striated. Muscles are often referred to as “sarco”, from the Greek word meaning strength. Therefore instead of saying cytoplasm one uses sarcoplasm. The endoplasmic reticulum in muscle types is called sarcoplasmic reticulum (SR). Sometimes authors instead of using “sarco” they say “myo”- myoplasm (cytoplasm, sarcoplasm). From histology you should remember that skeletal muscle cells are multinucleated. There are hundreds and hundreds of cells that are fused together into multinucleated structures called myotubes or myofibers. Myotubes, myofibers, and skeletal muscle cells are different words with the same meaning. They are huge cells that are centimeters in length and up to 200 m in diameter. They are attached to bones by tendons. Now if you look inside a single multinucleated muscle cell you will see that it is made up of myofibrils. There are hundreds of myofibrils inside a single muscle cell. Myofibrils are striated not in reality, but when you stain them with stains they become striated. There are dark bands and light bands therefore they are called “striated”. Each myofibril is composed of myofilaments. These myofilaments are either polymers of actin (thin filaments) or polymers of myosin (thick filaments). There is a central myosin filament and six actin filaments around it. Muscles are able to contract because these individual filaments slide on each other and come together. The sarcomere is the fundamental unit of contraction for skeletal and cardiac muscle. It is the area between two adjacent Z lines. The actin filaments come in from each side but they do not overlap. They are on top of each other but not overlapping because there has to space for them to slide in either direction. The H band is the space from where the actin, the thin filaments, end and where they begin again. It is free of actin and is composed only of myosin. It is the band that expands or contracts depending on where the actin filaments are. The dark bands are where the myosin and actin overlap. The light bands are where there are only actin filaments. Myosin, thick filaments, are large proteins consisting of 2 heavy chains and 4 light chains organized in a globular head called a cross-bridge and a long tail. The thick filaments are located in the center of the sarcomere and form the A band. The thin filaments are anchored into Z lines on both sides forming the I bands. Actin filaments have a polarity; there is a minus end and a plus end. Thin filaments are composed of actin, tropomyosin and troponin. Troponin is made up of 3 subunits: troponin I, troponin T and troponin C. Troponin is the regulatory protein that controls muscle contraction. Troponin I is inhibitory, troponin C binds calcium and troponin T interacts with tropomyosin. The sarcolemma which is the plasma membrane has invaginations which go into the muscle cell and T-tubules. T-tubules interact with the cisternae of the sarcoplasmic reticulum. There is one T-tubule in the middle and two cisternae on each end. This is called a TRIAD. The cisternae of the SR continues and if you imagine in 3D the SR surrounds each myofibril in its entirety. The T-tubules make specialized contact with these cisternae of the SR which allows communication between these two structures. In order for muscle cells to contract the Z lines have to come together. Muscle contraction is produced by the sliding of actin-rich filaments over the myosin-rich thick filament. The first thing to remember about skeletal muscles is that they are able to produce skeletal movement. In order to do this they have to connect to structures; skeletal muscles usually connect to bones by tendons. They are able to do this because each muscle cell is surrounded by a endomysium, perimysium and epimysium, connective tissues that allow skeletal muscle to connect to the bones. Dr. Hirsch told you that the physiologic control of skeletal muscles is simple because we only have motoneurons controlling contraction of skeletal muscles. There is a single neurotransmitter, acetylcholine. The nerve controls skeletal muscle contractions via acetylcholine. Skeletal muscles are innervated by myelinated motoneurons, usually the A type, 12-20 diameter and 70-120m/sec conduction velocity. We do not have the ability to make each muscle cell to contract slowly or quickly; each muscle cell contracts at a given speed. In order to go slow or fast I either have to use a few muscle cells or every muscle cell that I have here. Speed of contraction is proportional to the number of muscle cells engaged in contraction. This means that we can actually control them (voluntary control). Each motoneuron coming from the ventral horn of the spinal cord splits its axon into several endings. Each of these endings make contact with single muscle cells (motor unit). If I want to contract or move my arm slowly then I am using very few motor units. Fine movements (eye, hand, etc.) use 3-6 muscle fibers per motor unit. Each motor unit controls only a few muscle cells. For gross movements(back, posture) up to 100-150 muscle fibers/motor unit can be used. A single motor neuron controlling hundreds of muscle cells. When a muscle is excited with a single stimulus, the resulting contraction is called a TWITCH. The size of the twitch depends on the number of muscle fibers activated. The neurotransmitter is acetylcholine which is stored in vesicles. The action potential travels down a nerve terminal and depolarization opens VOLTAGE-GATED calcium channels on the neurolemma. Calcium flows into the neural terminal: it causes fusion of acetylcholine-containing vesicles with neurolemma and release of Ach. Into the cleft space (about 300 vesicles/impulse). Acetylcholine binds to nicotinic Ach-receptors (LIGAND-GATED) on the sarcolemma (MOTOR ENDPLATE). These channels open for about 1msec. Though they are not ion-selective, sodium is the main ion flowing inside the cell (30,000 Na/sec./channel). Acetylcholinesterase serves to break down acetylcholine which is then recycled and put back into vesicles. With the influx of sodium the sarcolemma in the motor endplate depolarizes. There is self-propagation (5m/sec) of action potentials along the sarcolemma due to the opening of VOLTAGE-GATED sodium channels. This lasts 3-5msec. The T-tubules, which are extensions of the sarcolemma, depolarize themselves. GRADED DEPOLARIZATIONS reach the triads probably because the T-tubules lack voltage-gated sodium channels. The sarcoplasmic reticulum is essentially a bank of calcium. There is a tremendous amount of calcium inside the SR. The concentration of calciium in the cytoplasm of any cell is very low. Muscle cells tend to keep calcium concentrations very, very low at 10 M. Internal membranes of the cell are polarized and can depolarize as well. The membrane of the T-tubule is a continuation of the cytoplasm of the cell membrane. Therefore the side of the membrane facing the cytosol would be negative; the outside would be positive. Depolarization induces conformational changes in voltage-sensitive protein on T-tubules. These proteins are mechanically coupled to calcium channels (RYANODINE CHANNELS) on the sarcoplasmic reticulum. Calcium channels than open. Since the sarcoplasmic reticulum stores calcium (in 20mM range), calcium rapidly flows from inside the SR to the myoplasm (myoplasmic [Ca ] raises from 10 to 10 M. The sarcoplasmic reticulum contains the protein CALSEQUESTRIN, which binds calcium and helps reduce “free” concentration of calcium from 20mM to 0.5 mM. Calcium channels remain open for a few milliseconds. While the concentration of calcium in the myoplasm is high, calcium interacts with troponin C. When calcium binds to the troponin C it allows the removal of the inhibitory action of troponin I. Troponin I blocks the affinity of actin to interact with myosin. When calcium binds to troponin C it induces conformational changes on troponin I and the myosin-binding site on actin is open (available for interaction with myosin). Contraction occurs because of crossbridge cycling. Each cycle moves actin-myosin about 5-10 nanometers. Muscle contraction is produced by the sliding of actin-rich thin filaments over the myosin-rich thick filament; this allows the Z lines to come closer together. The actin and the myosin filaments DO NOT TOUCH one another; they are not in contact with one another. Sliding is accomplished by the myosin heads (CROSS-BRIDGES) which attach to the actin filaments. The cross-bridges then bend, pulling the thin filaments over the thick filaments. The cross-bridges then detach, stand up and bind once more. The cross-bridge cycling continues for the duration of a muscle contraction.
CROSS-BRIDGE CYCLE 1. One molecule of ATP is hydrolyzed by each myosin head that bends 2. Calcium binds to troponin C, which induces conformational changes on troponin I, and myosin-binding site on actin is open (available for interaction with myosin).a. ADP + P are releasedb. Switch from 90 to 45 3. A new molecule of ATP must bind to the head at the end of the cycle in order for detachment to occur4. Hydrolysis and energy release induces the head to return to its perpendicular orientation- 45 to 905. Myosin ATPase is activated when the head attaches to actin, so that the energy is liberated only after myosin-actin interaction. *** RIGOR MORTIS: this occurs when the cross-bridge cycle stops after Step 26. At the conclusion of the action potential, the membrane repolarizes. The calcium permeability of the sarcoplasmic reticulum decreases and calcium is actively pumped back into the longitudinal tubules of the SR. 7. Contraction stops when the concentration of calcium in the myoplasm goes back to normal ( 10 M), i.e. within 3-=50msec. Calcium is pumped back into the SR by the calcium/magnesium pump (ATPase) on the SR membrane. As the [Ca ] is lowered, calcium dissociates from troponin. Troponion returns to its original configuration. Tropomyosin returns to its position blocking the myosin binding sites on actin. The cross-bridge cycling ceases and the muscle relaxes. What is a tetanus? It is the summation of contractile events. There is repeated neural stimulation (>50/sec.) You get a practical contraction. Practically speaking the calcium does not have time to go back into the sarcoplasmic reticulum and thus the [Ca ] in the myoplasm remains high. Wave after wave of depolarization along the T-tubules continues to keep those calcium channels open and therefore actin and myosin can continue their cross-bridge cycling. Relaxation, on the other hand, of the muscles is a passive phenomenon. Energy is not required to relax the muscles. The intrinsic elastic ability of the muscle allows it to re-extend itself. There is an exception to this and it is called RIGOR MORTIS. In order for the muscle to actually relax we have to have ATP. Why? The cross-bridge is bound to actin, to the actin-myosin interactions. In order to dislodge this interaction you need ATP. Once ATP binds the myosin cross-bridge can no longer bind to actin. If you don’t have ATP around the two proteins remain bound to one another. The muscles “freeze” in a given position in rigor mortis. (slide) CONTROL OF CONTRACTION 1. Modulation of Force = Recruitment of different numbers of Motor Units. This is because contraction of muscle fibers is an “all or none phenomenon”. Skeletal muscle cells either contract or they do not contract. There is no modulation. This will affect both the FORCE generated and the SPEED of contraction. In general, the smallest motor units are recruited first. This is called the SIZE PRINCIPLE.2. Muscle Fibers: They can be Slow or Fast. Example of fast muscles are the muscles of the arm or the fingers. Slow muscles can be found in the back or the neck. The difference between slow and fast muscles is exactly what the word is- slow or fast. All muscles are mixed; there are no pure “fast” muscles or “slow” muscles. All muscles are slow and fast mixed together and the percent of slow and fast components varies. Myosin is a protein and there is more than one gene that protein. Nature has chosen for skeletal muscle to have more than one gene for this protein. This protein is either a fast protein or a slow protein. The ATPase rate of that protein is either a fast ATPase or a slow ATPase. That is, it is a fast or a slow enzyme. The rate at which this isoenzyme can break down ATP is different. As a result you get skeletal muscle cells with either the fast or slow isoenzyme. Within each muscle cell there is only one type of myosin- slow or fast. Likewise each motor unit all the muscle cells within that motor unit are all fast or all slow, they are not mixed. There are two types of muscles. We have either red muscles which are slow or white muscles which are fast. Myoglobin content is very high in red muscle and very low in white muscle. Myoglobin stores oxygen. TYPE I (RED) II B WHITE II A RED *Myosinisoenzyme slow fast fast *oxidative cap.(# mitochondria) high low very high *glycolytic capacity moderate high high *diameter moderate large small *myoglobincontent high(red color) low MOTOR UNITS (* FIBERS IN EACH MOTOR UNIT ARE OF THE SAME TYPE) TYPE I TYPE II Nerve diameter small largeConduction velocity fast very fastNumber of fibers few manyForce of Unit low highMetabolic profile oxidative glycolyticContraction velocity moderate fastFatigability low high In terms of conduction the larger the nerves are in size or diameter, the faster they conduct impulses. If you need to get out of a room because there is a fire ,you want very large motor units to get you out of there. He then just ran through the rest out loud comparing type I to type II. MECHANICAL PARAMETERS IN MUSCLE CONTRACTION Units (force necessary to give acceleration: 1. Force Newton (n) 1kg/sec.)2. Length Meter (m)3. Time second (s) DERIVED VARIABLES: VELOCITY m/sec change in length/time unit WORK n m force x distance W = F DPOWER n m/sec work/time STRESS N/M force/cross area of muscleHaving giving you these derived variables definitions now you can understand the two major relationships physiologists use to measure the contraction of skeletal muscle cells. The first is called the Force-Length Relationship and the second is called the Velocity-Stress Relationship. Isometric means there is no change in length; the length is pre-established. The initial length of the muscle is called the PRELOAD. If I vary the preload what can the muscle do? If I vary the length will the muscle’s ability to contract change? Therefore we call this the Force-Length Relationship or the Stress-Preload Relationship. In the Velocity-Stress Relationship you vary the weights. Before we varied the length and here we are changing the weights we measure what the muscle can do. If we vary the weights how fast can this muscle contract? The preload is the initial length of the muscle. What we call AFTERLOAD is the stress or force generated by the muscle. Where the muscle is able to produce maximum stress is the ideal position. Contractions are proportional to the interactions between actin and myosin. The more interactions you have the more that muscle will produce stress and force. At its absolute best all the sarcomeres in that skeletal muscle are all at their very best. What do I mean by the very best? It is maximal overlap between actin and myosin. When you exceed that overlap either because the thin filaments are crashing against each other or the actin and myosin are barely even touching. Either the sarcomeres are too short or they are too long. At either of these situations the muscle is not performing at its best. The best is again somewhere in the middle.