#1 20. physiology. Muscle tissue 30/9/2015. Ahmad Adel Sallal. Mohammad Qudah
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1 # 20 physiology Muscle tissue Ahmad Adel Sallal 30/9/205 Mohammad Qudah
2 MUSCLES PHYSIOLOGY Awn, welcome to the first physiology lecture in the MSS, I wish you a perfect exams with high grades, and never forget: Do something today that your future self will thank you for. In this lecture, we ll discuss the function, types, structure and characteristics of the muscles, with highlighting the major mechanical events occur, our focus will be on skeletal muscles in this system at all. This lecture contains so many picture and animations, you have to really look at to understand, I ll write what s mentioned in animation video. Joint Stabilization Movement Muscles functions Posture Maintenance Thermogenesis Movement (the main function): by the contraction 2 of the muscle. Depends on type of muscle tissue 3 Depends on location of muscle tissue (GIT\Vessels etc.) Joint Stabilization: Movement may harm our joints so muscles function in stabilizing them. Posture Maintenance: muscles play a major role in keeping our body balanced. E.g. the muscle of the back. Protection Thermogenesis: muscles allow us to produce heat in the process of contraction, when there s utilization of energy (ATP hydrolysis), part of this energy will be dissipated as heat. Protection: Protection of the internal organs by the anterior and the posterior abdominal wall, also movement (running away from harm) might be a protection mechanism. Muscles also can store and move the substances within. About 40% of our body is skeletal muscles and almost another 0% is smooth and cardiac muscles. 2 Physiologically: contraction doesn t mean shortening, it s about activating the muscle. 3 E.g. - skeletal muscle by contraction will move one bone relative to the others, when smooth muscles present inside hollow organs like vessels and play a major role in controlling the pressure inside.
3 MUSCLE TISSUE CHARACTERISTICS: All types of muscle tissues share same basic characteristics: Excitability: the only two excitable tissues in the human body are muscles and nerves, excitability means the capacity of muscle to respond to a stimulus, in other words: the cell type have the ability to change its membrane potential (undergo the action potential), in order to perform contraction. Contractility: ability of a muscle to shorten and developing pulling force: The primary action of a muscle is to contract in order to activate the muscle because activation can produce force. Elasticity: ability of muscle to recoil to original resting length after stretching. Extensibility: the capability of being stretched. Classification of Muscle: According to fine structure, neuronal control and anatomically: Smooth\visceral Striated (skeletal\cardiac) Smooth (No striae) Voluntary (SNS) Involuntary (ANS) Skeletal Cardiac (Heart) Notice the large size of fibers 2
4 SKELETAL MUSCLES: Our focus will be on skeletal muscles, this picture shows the whole anatomical structure of skeletal muscle which enclosed by CT, and has blood\nerve supply to keep it active. The whole muscle tissue called muscle fascicles, which composed of multi muscle fibers where you find the cells itself arranged and extended longitudinally within. Like any cell in our body, muscle cells composed of plasma membrane (sarcolemma) and Cytoplasm (sarcoplasm) which contains endoplasmic reticulum (sarcoplasmic reticulum) and multiple nuclei. T-tubule (or transverse tubule) is a deep invagination of the sarcolemma. Inside the sarcoplasm there s myofibrils, a basic rod-like unit of a muscle cell, composed of long proteins 2 such as actin, myosin, and titin, and other proteins that hold them together. Invaginations allow depolarization of the membrane to quickly penetrate to the interior of the cell. 2 These proteins are the major player in contraction process, ACTIN, MYOSIN, TITIN, these proteins are organized into thin filaments and thick filaments, which repeat along the length of the myofibril. 3
5 Again: Each muscle fiber is multinucleated and behaves as a single unit, it contains bundles of myofibrils, surrounded by SR and invaginated by transverse tubules (T tubules). Each myofibril contains interdigitating Thick and thin filaments arranged longitudinally in sarcomeres. This picture clearly shows the innervation in order to stimulate muscles, blood supply to provide nutrition and gases, muscle fascicle and myofibrils. Large, multinucleated and striated In this picture, you can notice the multinucleated muscle fiber, the contractile proteins (mainly the thick and thin filaments) arranged in series, the sarcoplasmic reticulum encases the myofibril and the invaginations which are the T-tubules. In the histology of skeletal muscle, a triad is the structure formed by a T tubule with a sarcoplasmic reticulum (SR) known as the terminal cisterna on either side. Also within the sarcoplasm you can see these small mitochondria, the muscle tissue needs a lot of them in order to produce energy to complete the process of contraction. one T tubule and two terminal cisternae 4
6 SUMMARY: INTERNAL ORGANIZATION OF MUSCLE FIBERS. The sarcolemma The cell membrane of a muscle fiber (cell) Surrounds the sarcoplasm (cytoplasm of muscle fiber) A change in transmembrane potential begins contractions 2. Transverse tubules (T tubules) Transmit action potential through cell Allow entire muscle fiber to contract simultaneously Have same properties as sarcolemma 3. Myofibrils Lengthwise subdivisions within muscle fiber Made up of bundles of protein filaments (myofilaments) Myofilaments are responsible for muscle contraction 4. Types of myofilaments: thin filaments: Made of the protein actin thick filaments: Made of the protein myosin Z line Z line 5. Sarcoplasmic reticulum (SR) A membranous structure surrounding each myofibril Helps transmit action potential to myofibril Similar in structure to smooth endoplasmic reticulum Forms chambers (terminal cisternae) attached to T tubules 6. Triad Is formed by one T tubule and two terminal cisternae. Cisternae: Release Ca 2+ into sarcomeres to begin muscle contraction Note: The appearance of the skeletal muscle under microscope is striated. 5
7 SARCOMERE (THICK AND THIN): THE FUNCTIONAL UNIT Under the microscope The sarcomere is the basic unit of striated muscle tissue. Muscle cells are composed of tubular myofibrils, myofibrils are composed of repeating sections of sarcomeres, which appear under the microscope as dark and light bands. Sarcomeres are composed of long, fibrous proteins that slide past each other when the muscles contract and relax, these proteins are either thick (myosin) or thin (actin). A sarcomere is defined as the segment between two neighboring Z-lines. A band: An A-band contains the entire length of a single thick filament. I band: Surrounding the Z-line is the region of the I-band (for isotropic). I-band is the zone of thin filaments that is not superimposed by thick filaments. M Lines and Z Lines: M line: the center of the A band, at midline of sarcomere Z lines: the centers of the I bands, at two ends of sarcomere Zone of overlap: where thick and thin filaments overlap. The densest, darkest area on a light micrograph. The H Zone: the area around the M line has thick filaments but no thin filaments. Hexagonal area: look at the picture above, exactly at the 3 arrows, this shape is hexagonal, which means each thick filament is surrounded by 6 thin filaments, and each thin filament is surrounded by triangle of 3 thick filaments. What s the importance of this shape??! 2 There s two thin filaments in each sarcomere (Note the thick myosin filaments are between overlapping actin filaments) 2 Provide a huge amount of overlapping, which means more interactions between the thick and thin filaments. (Powerful interaction) 6
8 GENERAL MECHANISM OF SKELETAL MUSCLE CONTRACTION As we said before, the muscle tissues are Excitable, it s capable to respond to a stimulus, the stimuli is electrical signals carried by the motor-neurons in the area of neuromuscular junction. So once we have an action potential, the electrical signals will be in the form of an action potential motor-neurons, reaching the nerve terminal; this will lead to release of chemical substance called neurotransmitters; those neurotransmitters will activate the sarcolemma, activation of the skeletal muscle will result in depolarization, this depolarization t will travel in both directions, and deep in the invagination (t-tubules) to reach the sarcoplasmic reticulum. The sarcoplasmic reticulum will respond by releasing Calcium, calcium will convert the electrical signals into mechanical signals, this will lead to a process called excitation contraction coupling. The final signal in skeletal muscle contraction is??! So, in relaxed muscle actin and myosin lie side by side and H zones\i bands at its maximum width, during contraction, actins and myosins interact, the actins are pulled toward the center of each myosin myofilament. As a result the sarcomeres shorten. In the fully contracted muscle, the end of the actins overlap, the H zones disappear and the I band become very narrow. Elevation of myoplasmic calcium. 7
9 MYOSIN STRUCTURE: In order to understand the process more, we have to know the exact structure of the sarcomere and the filaments within. (Mainly myosin) Tail Head Myosin molecule consists of 6 proteins that make: tail, hinge and heads, two of these proteins are heavy chains (high molecular weight) and four of them is light chain (low molecular weight). The head: binds the filamentous actin, and uses ATP hydrolysis to generate force and to "walk" along the filament made of two globular protein subunits, reaches the nearest thin filament. Heads contain active sites for: ) Actin 2) ATP (energy for mechanical work). Note: Titin is a giant protein that serves as a template for myosin assembly, titin strands recoil after stretching. The two tails are in the center of the sarcomere (with M line), their function is to binds to other myosin molecules Notice that the area doesn t have myosin head projections M line Function: stabilize the myosin filaments theorized to aid in transmission of force from sarcomere to cytoskeletal intermediate filaments In the peripheral points of myosin, you can notice that there s a lot of head projections, these head projections will function in the process of overlapping between the thick and the thin filaments, there normal shape is like projecting outward, each myosin head contain site for actin. 300 heads for every myosin molecule. 8
10 ACTIN STRUCTURE: Thin filaments anchored at the Z lines, and present in the I bands, interdigitate with the thick filaments in a portion of the A band. Thin filaments are composed of: F actin= filamentous actin G-actin molecules in a helical arrangement (contain myosin binding sites) G-actins bind to each other forming F actin, thin two of these F actin binds forming the Double helical actin strands Nebulin: Filament that forms internal support and attachment for actin Tropomyosin filaments (rod shaped) over the myosin binding sites. Troponin (complex of three molecules ) it s a regulatory protein that permits cross-bridge formation when it bind to calcium. Attached to tropomyosin (Has binding sites for Ca 2+ ). We said that contraction is the interdigitations that result from the binding of Myosin head with Actin filaments, there will be sliding of the thick over the thin filaments, interdigitations. By the cycle of attachment-detachment, the thick filament will bring the thin filament to the center of the sarcomere and this will increase the overlapping. When the binding sites are covered by Tropomyosin, so there is no interaction between Actin and Myosin, upon stimulation and Ca+2 releasing (Ca+2 reach specific threshold) it will bind with Troponin C. Troponin C will change its shape (conformational change), this will alter Troponin I & T shape, Tropomyosin is removed from the binding site, and Myosin can bind Actin, this process needs energy. Test yourself: what do we mean by partially contracted Sarcomere??! 2 Q: Which filament has moved as the sarcomere contracted? 3 Troponin T\I\C and each one has its own function. I = inhibition= no interaction C : will bind to Ca+2, T: contacts with Tropomyosin 2 Low calcium duration 3 The thick myosin filaments have not changed, but the thin actin filaments have moved closer together. 9
11 MUSCLE CONTRACTION, MECHANICAL EVENTS: ACTO-MYOSIN CROSS BRIDGE CYCLE We said before that myosin head has a binding site for actin and ATP, myosin head itself is an enzyme that has an internal capability to hydrolyze ATP, its called actin activated ATPase enzyme. This means that actin will accelerate the hydrolysis of ATP by ATPase activity of myosin head. So: Myosin heads bind to actin filaments. ATP hydrolysis allows the myosin head to walk along the actin filament and provided the energy needed for the mechanical movement: Attachment pulling detachment attachment again etc... Myosin is an Actin-activated ATPase. The binding of Actin-Myosin will increase the speed of ATP Cleavage increase in Attachment-Detachment cycle Step: Active site exposure + Step2: Cross-bridge formation: At rest Myosin head will bind with one molecule of ATP. ATP will be cleaved into ADP +Pi Energy release. ATP energy used to charge the myosin head. (Change the confirmation of it in order to increase affinity for the binding site) When there s a stimulus: The CA ions bind to the troponin C, This binding weakens troponin-tropomoysin complex, and actin Troponin molecule changes position, rolling the tropomyosin away from the active sites on actin, thus allowing them to interact with energized myosin heads 2. The strength of contraction depends on the amount of cross bridge formation which depends on the amount and duration of Ca+2 in the cytosol. With the active sites on the actin exposed, the myosin heads bind to the, forming cross-bridges. 2 The myosin head will remain in this conformational as long as ADP+Pi are attached. 0
12 Step3: Pivoting of myosin head: -myosin cross bridge attaches to the actin myofilaments. - Power stroke: the myosin head pivots and bends as it pulls on the actin filament, pulling it toward the M line. *meanwhile ADP +p are released. - As new ATP attaches to myosin head, the cross bridge detaches. - As ATP is split into ADP and P, cocking of the myosin head occurs. Rigor Mortis: is one of the recognizable signs of death, caused by chemical changes in the muscles after death, to be more precise, In the absence of ATP, the muscles remain in a contraction state as the myosin head stayed attached to actin ( ATP is the cause of separation) and this what Happens the muscles of the body after death The DR will continue this step with the others in the next lecture, Insha Allah. If you want to thank me, study this sheet another time! Best wishes Your brother: Ahmad Adel Sallal
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