Muscle Physiology PDF

General PhysiologyDr. Iyden Kamel Muscle Physiology Three types of muscle tissue in mammals can be distinguished on the basis of morphological and functional characteristics. Skeletal muscle is composed of bundles of very long, cylindrical, multinucleate...

General PhysiologyDr. Iyden Kamel Muscle Physiology Three types of muscle tissue in mammals can be distinguished on the basis of morphological and functional characteristics. Skeletal muscle is composed of bundles of very long, cylindrical, multinucleated cells that show cross-striations. Cardiac muscle also has cross-striations and is composed of elongated, branched individual cells that lie parallel to each other. At sites of end-to-end contact are the intercalated disks, structures found only in cardiac muscle. Contraction of cardiac muscle is involuntary, vigorous, and rhythmic. Smooth muscle consists of collections of fusiform cells that do not show cross-striations. Their contraction process is slow and not subject to voluntary control. Some muscle cell organelles have names that differ from their counterparts in other cells. The cytoplasm of muscle cells (excluding the myofibrils) is called sarcoplasm, and the smooth endoplasmic reticulum is called sarcoplasmic reticulum. The sarcolemma is the cell membrane. Skeletal Muscle All skeletal muscles are composed of numerous bundles (fasculi) of muscle fibers; that are made up of successively smaller subunits called myofibrils. Except for about 2 per cent of the fibers, each fiber is usually innervated by only one nerve ending, located near the middle of the fiber. Cross-Striation Muscle fibers show cross-striations of alternating light and dark bands. The darker bands are called A bands; the lighter bands are called I bands. In the electron microscope, each I band is bisected by a dark transverse line, the Z line. The unit extends from Z line to Z line called the sarcomere. 1 General PhysiologyDr. Iyden Kamel Structure of Myofibrils Electron microscope shows that each myofibril consists of two types of filaments, thick and thin myofilaments: 1. Thick Filament: Each thick filament contains several hundred myosin molecules; each molecule has two globular heads and a long tail. The heads of the myosin molecules form cross-bridges with actin. Myosin contains heavy chains and light chains, and its heads are made up of the light chains and the amino terminal portions of the heavy chains. These heads contain an actin-binding site and a catalytic site that hydrolyzes ATP. The M line is the site of cross connections that hold the thick filaments in proper array. 2. Thin Filament: The thin filaments are polymers made up of two chains of actin that form a long double helix. Tropomyosin molecules are long filaments located in the groove between the two chains in the actin. Troponin molecules are small globular units located at intervals along the tropomyosin molecules. Each of the three troponin subunits has a unique function: Troponin T binds the troponin components to tropomyosin; troponin I inhibits the interaction of myosin with actin; and troponin C contains the binding sites for the Ca2+ that helps to initiate contraction. The contractile mechanism in skeletal muscle largely depends on the proteins myosin, actin, tropomyosin, and troponin. Troponin is made up of three subunits: troponin I, troponin T, and troponin C. These proteins are collectively known as contractile proteins. The function of these proteins is regulated by other proteins called regulatory proteins which include: 1. Actinin: That binds actin to the Z lines. 2. Titin: Which is the largest known protein serves to connect the Z lines to the M lines. 3. Desmin: That binds the Z lines to the plasma membrane. 2 General PhysiologyDr. Iyden Kamel Sarco-tubular System: The muscle fibrils are surrounded by structures made up of membranes that appear in electron photomicrographs as vesicles and tubules. These structures form the sarcotubular system, which is made up of T system and a sarcoplasmic reticulum. 1. The T system It is a transverse tubule continuous with the sarcolemma of the muscle fiber, forms a grid perforated by the individual muscle fibrils.The space between the two layers of the T system is an extension of the extracellular space. The T system provides a path for the rapid transmission of the action potential from the cell membrane to all the fibrils in the muscle. 2. The sarcoplasmic reticulum, It forms irregular enlarged terminal cisterns around each of the fibrils, in close contact with the T system at the junctions between the A and I bands. The sarcoplasmic reticulum is an important store of Ca2+ and also participates in muscle metabolism. At these points of contact, the arrangement of the central T system with a cistern of the sarcoplasmic reticulum on either side has led to the use of the term triads to describe the system. Neuro-Muscular Junction As the axon supplying a skeletal muscle fiber approaches its termination, it loses its myelin sheath and divides into a number of terminal buttons, or end-feet. The end-feet contain many small, clear vesicles that contain acetylcholine, the transmitter at these junctions. The endings fit into junctional folds, which are depressions in 3 General PhysiologyDr. Iyden Kamel the thickened portion of the muscle membrane at the junction. The space between the nerve and the thickened muscle membrane is comparable to the synaptic cleft. The whole structure is known as the neuromuscular junction or motor end plate. Excitation-Contraction Coupling It is important to distinguish between the electrical and mechanical events in muscle. Muscle fiber membrane depolarization normally starts at the motor end plate then the action potential is transmitted along the muscle fiber and initiates the contractile response. The sliding theory is the most acceptable theory that explain contraction and relaxation response of skeletal muscle in sequence events as follow: A. Steps in contraction: (1) The impulse arriving in the end of the motor neuron increases the permeability of its endings to Ca2+ that enter the endings and triggers the exocytosis of the acetylcholine-containing vesicles. Lambert–Eaton syndrome (muscle weakness) is caused by antibodies against one of the Ca2+ channels in the nerve endings at the neuromuscular junction and decreases acetylcholine release. (2) The acetylcholine diffuses to the muscle fiber receptors, which are concentrated at the tops of the junctional folds of the membrane in the motor end plate and Binds with them. Myasthenia gravis is a serious fatal disease in which skeletal muscles are weak and tire easily. It is caused by the formation of circulating antibodies to the acetylcholine receptors that destroy some of these receptors. (3) Binding of acetylcholine to these receptors initiates influx of Na+ that produce a depolarizing potential in the end plate. Acetylcholine is then removed from the synaptic cleft by acetylcholine-esterase, which is present in high concentration at the neuromuscular junction. (4) Action potentials are conducted away from the end plate in both directions along the muscle fiber until reach to the sarco-tubular system (triad) and initiate the cisternae of sarcoplasmic reticulum to release their storage of calcium ions into sarcoplasm. 4 General PhysiologyDr. Iyden Kamel (5) When the Ca2+released by the action potential binds to troponin C, the binding of troponin I to actin is weakened, and this permits the tropomyosin to move laterally. This movement uncovers binding sites for the myosin heads. ATP is then split and contraction occurs by formation of cross-linkages between actin and myosin and sliding of thin on thick filaments, producing movement. B. Steps in Relaxation: (1) Ca2+ pumped back into sarcoplasmic reticulum by active transport. (2) Once the Ca2+ concentration outside the reticulum has been lowered sufficiently, chemical interaction between myosin and actin ceases and the muscle relaxes. Note that ATP provides the energy for both contraction and relaxation. If transport of Ca2+ into the reticulum is inhibited, relaxation does not occur even though there are no more action potentials; the resulting sustained contraction is called a contracture. The Muscle Twitch A single action potential causes a brief contraction followed by relaxation. This response is called a muscle twitch. The twitch starts about 2 ms after the start of depolarization of the membrane, before repolarization is complete. The duration of the twitch varies with the type of muscle being tested. "Fast" muscle fibers have twitch durations as short as 7.5 ms. "Slow" muscle have twitch durations up to 100 ms. 5 General PhysiologyDr. Iyden Kamel Summation of Contractions Because the contractile mechanism does not have a refractory period, repeated stimulation before relaxation has occurred produces additional activation of the contractile elements and a response is known as summation of contractions. With rapidly repeated stimulation, activation of the contractile mechanism occurs repeatedly before any relaxation has occurred, and the individual responses fuse into one continuous contraction. Such a response is called tetanus (tetanic contraction). It is a complete tetanus when no relaxation occurs between stimuli and an incomplete tetanus when periods of incomplete relaxation take place between the summated stimuli. Types of Contraction 1. Isometric Contraction: It occurs without an appreciable decrease in the length of the whole muscle. Since work is the product of force times distance, isometric contraction do not do work. 6 General PhysiologyDr. Iyden Kamel 2. Isotonic Contraction: Contraction against a constant load, with approximation of the ends of the muscle, isotonic contractions do work. Muscle Types Skeletal muscle is a very heterogeneous tissue made up of fibers that vary in myosin ATPase activity, contractile speed, and other properties. The fibers fall roughly into two types, type I and type II. 1. Red muscles: They contain many type I fibers which are darker than other muscles due to their high containing of myoglobin. They respond slowly and have a long latency, thus they are adapted for long, slow, posture-maintaining contractions. The long muscles of the back are red muscles. 2. White muscles: They contain mostly type II fibers with less content of myoglobin and have short twitch durations. They are specialized for fine, skilled movement. The extra-ocular muscles and some of the hand muscles contain many type II fibers and are generally classified as white muscles. Energy Sources : Muscle contraction requires energy, and muscle has been called "a machine for converting chemical energy into mechanical work." The immediate source of this energy is ATP. ATP + H2O → ADP + Phosphate + 7.3 Kcal ATP molecules are formed by the metabolism of carbohydrates and lipids which include: 1. Aerobic metabolism of glucose: 7 General PhysiologyDr. Iyden Kamel Glucose + 2 ATP (or glycogen + 1 ATP) oxygen 6 CO2 + 6 H2O + 40ATP 2. Oxidation of free fatty acids: FFA Oxygen CO2 + H2O + ATP 3. Hydrolysis of phosphoryl creatine: Phosphoryl Creatine + ADP Creatine + ATP 4. Anaerobic metabolism of glucose Glucose + 2 ATP (or glycogen + 1 ATP) Anaerobic 2 Lactic acid + 4 ATP The Oxygen Debt Mechanism Use of the anaerobic pathway causes enough accumulation of lactate in the muscles and produces an enzyme-inhibiting decline in PH. After a period of exertion is over, extra O2 is consumed to remove the excess lactate, replenish the ATP and phosphorylcreatine stores, which is knwon oxygen debt. Trained athletes are able to increase the O2 consumption of their muscles to a greater degree than untrained individuals and are able to utilize FFA more effectively. Because of this, they contract smaller oxygen debts for a given amount of exertion. When muscle fibers are completely depleted of ATP and phosphoryl creatine, they develop a state of rigidity called rigor. When this occurs after death, the condition is called rigor mortis. Types of Smooth Muscle The smooth muscle of each organ is distinctive from that of most other organs in several ways: (1) physical dimensions, (2) organization into bundles or sheets, (3) response to different types of stimuli, (4) 8 General PhysiologyDr. Iyden Kamel characteristics of innervation, and (5) function. Yet for the sake of simplicity, smooth muscle can generally be divided into two major types, multi-unit smooth muscle and unitary (or single-unit) smooth muscle. Regulation of Contraction by Calcium Ions As is true for skeletal muscle, the initiating stimulus for most smooth muscle contraction is an increase in intracellular calcium ions. This increase can be caused in different types of smooth muscle by nerve stimulation of the smooth muscle fiber, hormonal stimulation, stretch of the fiber, or even change in the chemical environment of the fiber. Yet smooth muscle does not contain troponin, the regulatory protein that is activated by calcium ions to cause skeletal muscle contraction. Instead, smooth muscle contraction is activated by an entirely different mechanism, as follows. Calcium Ions Combine with Calmodulin to Cause Activation of Myosin Kinase and Phosphorylation of the Myosin Head. 9 General PhysiologyDr. Iyden Kamel In place of troponin, smooth muscle cells contain a large amount of another regulatory protein called calmodulin. Although this protein is similar to troponin, it is different in the manner in which it initiates contraction. Calmodulin does this by activating the myosin cross-bridges. This activation and subsequent contraction occur in the following sequence. 1-The calcium ions bind with calmodulin. 2. The calmodulin-calcium complex then joins with and activates myosin light chain kinase, a phosphorylating enzyme. 3. One of the light chains of each myosin head, called the regulatory chain, becomes phosphorylated in response to this myosin kinase. When this chain is not phosphorylated, the attachment-detachment cycling of the myosin head with the actin filament does not occur. 10 General PhysiologyDr. Iyden Kamel Intracellular calcium ion (Ca++) concentration increases when Ca++ enters the cell through calcium channels in the cell membrane or the sarcoplasmic reticulum (SR). The Ca++ binds to calmodulin to form a Ca++-calmodulin complex, which then activates myosin light chain kinase (MLCK). The MLCK phosphorylates the myosin light chain (MLC) leading to contraction of the smooth muscle. When Ca++ concentration decreases, due to pumping of Ca++ out of the cell, the process is reversed and myosin phosphatase removes the phosphate from MLC, leading to relaxation. 11