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50.5: The physical interaction of protein filaments Is required for muscle function The types of effectors:Skeletal muscles .glands .smooth muscle * Muscle contraction is the product of microfilament movement powered by chemical energy. Vertebrate Skeletal Muscle: *They named skeletal because it is attach to a skeleton by a tendon. *They consist of thousands of muscle fibers arranged longitudinally and between them layers of connective tissue. *They are striated, long, surrounded by plasma membrane (sarcolemma), multinucleated (reflecting its formation by the fusion of many embryonic cells). *Each muscle consist of many microfibers *The muscle fibers are arranged longitudinally, parallel to each other. *Sacroplasm, nuclei, mitochondria, Sarcoplasmic reticulum are exist between microfibrils. *Each microfibril consists of microfilaments (myofilaments). *The microfilaments are arranged in a special way that is repeated along the myofibril we called sarcomere. Refer to figure 50.26 page 1150 *The sarcomere is the basic, structural, contractile unit of the muscle. *Each sarcomere is bordered by Z line (protein that anchors actin filaments). *In the middle of the sarcomere there are myosin filaments *The region in the middle of the sarcomere is called M line (proteins that anchor myosin filaments) 1 Lecture 19 50.5: The physical interaction of protein filaments Is required for muscle function *At rest there is a partially overlapping between actin and myosin.. Near the edge of the sarcomere there are only thin filaments, whereas the zone in the center contains only thick filaments. * A Band is a region of the myosin filaments length -- appear dark on the microscope *I Band Is a region between Z lines contain actin filaments -appear light on the microscope *H Band Is a region in the middle of the A Band -appear light on the microscope *The arrangement of the actin and myosin filaments is the key to how the sarcomere contract and this regular arrangement of the filaments create a pattern of light and dark bands (That is why we called it a striated muscle) Sliding-Filament model of muscle contraction *The whole muscle, muscle fibers, myofibril, shortens when they contact, but myofilaments (actin, myosin) they DON’T shorten instead they move past each other increasing their overlap. Refer to figure 50.27 page 1151 The structure of contractile filaments Thin filaments (actin): 1. Two twisted strands of actin monomers (each is a globular polypeptide)the filament is spherical 2. Two types of regulatory proteins : 2 Tropomyosin strands coiled around the actin.(at rest it covers the myosin-binding sites) Troponin complex bounded to the actin ,it consist of 3 subunits One binds to actin monomers One binds to Ca+2 One binds to tropomyosin 2 Lecture 19 50.5: The physical interaction of protein filaments Is required for muscle function At normal situations Ca+2 concentration is low in cytoplasm (It’s congregate in the extracellular fluid or the sarcoplasmic reticulum) *When Ca+2 bind to one Troponin subunit, a change in the conformation of the Troponin occurs, this lead to movement of tropomyosin to expose the myosin binding sites. *At the relaxation of the muscle, the Ca+2 is removed from the cytoplasm and returned to the extracellular fluid or the sarcoplasmic reticulum, and the myosin binding sites are covered again by the tropomyosin Refer to figure50.29 Page 1152 Thick filaments(myosin): *They are staggerd arrays of myosin molecules. *Eeach myosin molecule consist of 2 polypeptide.(every polypeptide has:) 1. Fibrous tail 2. Globular head(approximately 350 heads) *The head is a motor protein that changes it’s conformation when it takes energy (ATP) * There is 2 region on the myosin head :1. A region that binds to the myosin binding site on the actin filament to make a cross-bridge 2. A region that has ATPASE enzyme that hydrolysis ATP Figure 50.28 page 1151 *The myosin-actin interaction need a lot of ATP *ATP binds to head region then it’s hydrolyzed to ADP +inorganic phosphate * The energy released from ATP hydrolysis change the configuration of myosin head from low to high energy configuration *At the same time the myosin head binding site on the actin filament is exposed by the presence of the Ca+2 . 3 Lecture 19 50.5: The physical interaction of protein filaments Is required for muscle function *When the cross-bridge is formed, ADP +inorganic phosphate is released and myosin head return to the low energy configuration, so it pulls the actin to the middle of the sarcomere. * To break the cross- bridge we need ATP, then ATP binds to the myosin head and the cycle is repeated. * The skeletal muscles don’t contract unless they’re stimulated by a motor neuron remember the skeletal muscle is an excitable cell which means we can convert the electrical current in it to an action. *The 350 heads of the thick filament forms and re-forms about 5 crossbridges per second * The ATP that already exists is enough or only few contractions….To power repetitive contractions the muscle cell relies on 2 other storage compounds: 1. Creatine phosphate(Formed in the liver and pancreas) Transfer of phosphate group from creatine phosphate to ADP(an endergonic reaction) in an enzyme-catalyzed reaction synthesizes additional ATP- it can sustain contraction for 15 seconds *The hydrolysis of excess creatine produces Creatinine which is used for the kidney function test. 2. Glycologen The broken of glycologen to glycose generates ATP by either (aerobic respirationcan sustain contraction for nearly an hour) or by ( glycolosis it can sustain contraction for 1 minute ) The role of calcium and regulatory proteins Figure50.30page1153 *Each microfibril is surrounded by a sarcoplasmic reticulum * When action potential arrives to the synaptic terminals of a motor neuron, the acytelcholin (neurotransmitter) is released, and then it binds to the ligand gated ion channel on the muscle fiber leading to a depolarization. *The action potential spreads along the plasma membrane and down the Transfer (T) tubule ( infolding from the plasma membrane filled 4 Lecture 19 50.5: The physical interaction of protein filaments Is required for muscle function with the interstitial fluid and they’re located in specific sites in each skeletal muscle cell) * T tubule makes a close contact with sarcoplasmic reticulum SR *The action potential triggers Ca+2 release from SR by opening the Ca+2 channels in the membrane of the SR *Ca+2 bind to the Troponin complex, initiating contraction of the muscle fibers * When motor neuron input stops, the muscle cells relaxes Filaments slide back to their starting position Cytosolic Ca+2 is removed by Active transport using Ca+2 pump into SR. *some diseases cause paralysis by interfering with the excitation of the skeletal muscles by the motor neuron (at the neuromuscular junction): 1. amyotrophic lateral sclerosis ALS (also called Lou Gehrig’s disease): the motor neurons in the spinal cord and brainstem degenerate, and the muscle fibers with which they synapse atrophy. It’s progressive and fatal in 5 years after the symptoms appear no cure or treatment. 2. Myasthenia gravis (A type of autoimmune disease): a person produces antibodies to the acetylcholine receptors on skeletal muscle fibers, as the number of these receptors decreases, synaptic transmission between motor neurons and muscle fibers declines there are effective treatments. 3. Botulism: which is typically fatal because muscles required for breathing fail to contract when acetylcholine release is blocked also used in cosmetic procedures as BOTOX. 5 Lecture 19