Guyton Chap 6 - Contraction of skeletal muscle PDF

Contraction of Skeletal Muscle GUYTON -CHAPTER 6  PHYSIOLOGICAL ANATOMY OF SKELETAL MUSCLE About 40% of the body is skeletal muscle, another 10% is smooth and cardiac muscle. Skeletal muscles are composed of numerous fibers. Each of these fibers is made up of...

Contraction of Skeletal Muscle GUYTON -CHAPTER 6  PHYSIOLOGICAL ANATOMY OF SKELETAL MUSCLE About 40% of the body is skeletal muscle, another 10% is smooth and cardiac muscle. Skeletal muscles are composed of numerous fibers. Each of these fibers is made up of smaller subunits. Each fiber is usually innervated by only one nerve ending, located near the middle of the fiber.  The Sarcolemma - Membrane Enclosing a Skeletal Muscle Fiber The sarcolemma consists of a true cell membrane - plasma membrane, and an outer coat of polysaccharide material that contains collagen fibrils. At each end of the muscle fiber, sarcolemma fuses with a tendon fiber. The tendon fibers into bundles muscle tendons that connect the muscles to the bones. Myofibrils -Composed of Actin and Myosin Filaments. Each muscle fiber contains several hundred- several thousand myofibrils. Each myofibril is composed of about 1500 myosin filaments and 3000 actin filaments- responsible for the muscle contraction. The thick filaments in the diagrams -myosin, the thin filaments are actin. The light bands contain only actin filaments-I bands -isotropic to polarized light. The dark bands contain myosin filaments, and the ends of the actin filaments, where they overlap the myosin -A bands -anisotropic to polarized light (beam splitters). Small projections from the sides of the myosin filaments are cross-bridges; interaction between these cross-bridges and the actin filaments cause contraction. Titin Filamentous Molecules Keep the Myosin and actin Filaments in Place. The side-by-side relationship between the myosin and actin filaments is maintained by a large number of filamentous molecules of a protein –titin; one of the largest protein molecules in the body; very springy. Titin molecules holds the myosin and actin filaments in place.  Sarcoplasm - Intracellular Fluid Between Myofibrils. Spaces between the myofibrils are filled with sarcoplasm, containing K, Mg, phosphate, protein enzymes; mitochondria. Mitochondria supply the contracting myofibrils with energy in the form of adenosine triphosphate (ATP). Sarcoplasmic Reticulum - regulating Ca storage, release, reuptake and therefore muscle contraction.  GENERAL MECHANISM OF MUSCLE CONTRACTION  1. An action potential travels along a motor nerve to its endings on muscle fibers.  2. At each ending, the nerve secretes a small amount of neurotransmitter acetylcholine.  3. Acetylcholine acts on a muscle fiber membrane to open acetylcholine-gated cation channels.  4. The opening of acetylcholine-gated channels allows large quantities of Na ions to diffuse to the interior of the muscle; local depolarization opens voltage-gated Na channels, which initiates an action potential at the membrane.  5. The action potential travels along the muscle fiber in the same way that action potentials travel along nerve fiber membranes.  6. The action potential depolarizes the muscle membrane, sarcoplasmic reticulum releases large quantities of Ca ions.  7. The Ca ions initiate attractive forces between the actin and myosin filaments, causing them to slide alongside each other -contractile process.  8. After a fraction of a second, the Ca ions are pumped back into the sarcoplasmic reticulum by a Ca2+ membrane pump and remain stored in the reticulum until a new muscle action potential comes along; removal of Ca from the myofibrils causes the muscle contraction to cease. Myosin Filaments Are Composed of Multiple Myosin Molecules The myosin molecule - composed of 6 polypeptide 2 heavy chains, 4 light chains. The heavy chains form tail of the myosin molecule. One end of each of these chains is folded into a globular structure - myosin head. The light chains are also part of the myosin head, two to each head. These light chains help control the function of the head during muscle contraction. The myosin filament is made up of 200 or more individual myosin molecules. The protruding arms and heads together - cross-bridges. Each cross-bridge is flexible at two points – hinges and where the head attaches to the arm. The hinged arms allow the heads either to be extended from the body of the myosin filament or brought close to the body. ATPase Activity of the Myosin Head. Myosin head functions as an adenosine triphosphatase (ATPase) enzyme; cleave ATP and use the energy derived from the ATP’s high-energy phosphate bond to energize the contraction process.  Actin Filaments Are Composed of Actin, Tropomyosin, and Troponin The backbone of the actin filament is a double-stranded F-actin protein molecule. The two strands are wound in a helix. Each strand of F-actin helix is composed of G- actin molecules. Attached to each G-actin molecules is one molecule of ADP. ADP molecules- interact with cross-bridges of the myosin filaments to cause muscle contraction.  Tropomyosin Molecules Wrapped spirally. In the resting state, tropomyosin molecules lie on top of the active sites of the actin strands - attraction cannot occur between actin and myosin filaments to cause contraction. Contraction occurs only when an appropriate signal causes a conformation change in tropomyosin that “uncovers” active sites on the actin molecule and initiates contraction.  Troponin – role in Muscle Contraction Attached along the sides of the tropomyosin molecules- troponin. These protein molecules are complexes of 3 loosely bound protein subunits. Troponin I subunit -affinity for actin, troponin T- for tropomyosin, troponin C- for Ca ions. This complex attachs tropomyosin to the actin. The strong affinity of the troponin for Ca ions initiates contraction process.  Interaction of One Myosin Filament, Two Actin Filaments, and Ca Cause Contraction  A pure actin filament without the presence of the troponin-tropomyosin complex (in the presence of magnesium ions and ATP) binds instantly and strongly with myosin molecules.  If the troponin-tropomyosin complex is added to the actin filament, the binding between myosin and actin does not take place.  Active sites on the normal actin filament of the relaxed muscle are inhibited or physically covered by the troponin-tropomyosin complex; the sites cannot attach to the heads of the myosin filaments to cause contraction. Activation of the Actin Filament by Ca Ions In the presence of large amounts of Ca, inhibitory effect of the troponin-tropomyosin on the actin filaments is inhibited. Ca combines with troponin C, troponin complex undergoes a conformational change, moves tropomyosin and uncovers the active sites of the actin, allowing active sites to attract the myosin cross-bridge heads and allow contraction to proceed. Interaction of the Activated Actin and Myosin Cross-Bridges— The Walk-Along Theory of Contraction. As soon as the actin filament is activated by the Ca ions, the heads of myosin filaments become attracted to the active sites of the actin and initiate contraction. One hypothesis -walk-along theory of contraction. When a head attaches to an active site, it causes changes in the intramolecular forces between the head and arm of its cross-bridge.  ATP -Energy Source for Contraction When a muscle contracts, work is performed, and energy is required. Large amounts of ATP are cleaved to form ADP during the contraction process, and the more work performed by the muscle, the more ATP is cleaved -Fenn effect. In the absence of ATP, myosin heads will not detach, causing rigor mortis. This cycle will continue as long as ATP is available and Ca2" is bound to troponin. If ATP is not available, the cycle stops between steps 2 & 3.  Effect of Muscle Length on Force of Contraction in the Whole Intact Muscle  The whole muscle has a large amount of connective tissue in it; the sarcomeres in different parts of the muscle do not always contract the same amount.  When the muscle is at its normal resting length, at a sarcomere length of about 2 micrometers, it contracts on activation with the approximate maximum force of contraction. However, the increase in tension that occurs during contraction-active tension, decreases as the muscle is stretched beyond its normal length— to a sarcomere length greater than about 2.2 micrometers.  Relation of Velocity of Contraction to Load A skeletal muscle contracts rapidly when it contracts against no load. When loads are applied, the velocity of contraction decreases progressively as the load increases. When the load has been increased to equal the maximum force that the muscle can exert, the velocity of contraction becomes zero, and no contraction results, despite activation of the muscle fiber. ENERGETICS OF MUSCLE CONTRACTION Work Output During Muscle Contraction When a muscle contracts against a load, it performs work. To perform work means that energy is transferred from the muscle to the external load to lift an object to a greater height or to overcome resistance to movement. W = L ×D W - work, L - load, D - distance of movement against the load.  Three Sources of Energy for Muscle Contraction  Most of the energy required for muscle contraction is used to pull the actin filaments, but small amounts are required for : (1) pumping Ca from the sarcoplasm into the sarcoplasmic reticulum after the contraction is over; (2) pumping Na and K ions through the muscle fiber membrane to maintain an appropriate ionic environment for the propagation of muscle fiber action potentials.  The concentration of ATP in the muscle fiber maintains full contraction for only 1 to 2 seconds at most.  The ATP ADP, transfers energy to the contracting machinery of the muscle fiber. Then, ADP is rephosphorylated to new ATP within another fraction of a second, which allows the muscle to continue its contraction.  3 sources of the energy for ADP rephosphorylation Source of energy to reconstitute the ATP- phosphocreatine -carries a high-energy phosphate bond similar to the bonds of ATP. Slightly higher amount of free energy than that of each ATP bond. Therefore, phosphocreatine is instantly cleaved, and its released energy causes bonding of a new phosphate ion to ADP to reconstitute the ATP.  Total amount of phosphocreatine in the muscle fiber is also small, 5 times as great as the ATP.  Combined energy of both the stored ATP and phosphocreatine causing maximal muscle contraction for only 5 to 8 seconds.  2 nd Source of energy used to reconstitute ATP and phosphocreatine-glycolysis—breakdown of glycogen stored in the muscle cells.  Glycogen pyruvic acid and lactic acid liberates energy that is used to convert ADP to ATP; the ATP energizes additional muscle contraction and also to re-forms the stores of phosphocreatine.  The importance of this glycolysis  Glycolytic reactions can occur even in the absence of oxygen, so muscle contraction can be sustained for many seconds and up to more than 1 minute, even when oxygen delivery from the blood is not available.  Rate of ATP formation by glycolysis is about 2.5 times as rapid as ATP formation in response to cellular foodstuffs reacting with oxygen;  Many end products of glycolysis accumulate in the muscle cells, glycolysis loses its capability to sustain maximum muscle contraction after about 1 minute.  3rd source of energy- oxidative metabolism, combining oxygen with the end products of glycolysis and with cellular foodstuffs to liberate ATP.  More than 95% of all energy used by the muscles for sustained long-term contraction is derived from oxidative metabolism.  The foodstuffs: carbohydrates, fats, and protein. For extremely long-term maximal muscle activity— over many hours—the greatest proportion of energy comes from fats but, for periods of 2 to 4 hours, as much as one half of the energy can come from stored carbohydrates.  Efficiency of Muscle Contraction The percentage of the chemical energy in nutrients that can be converted into work is