BIOL 460 1st Edition Lecture 14Outline of Last Lecture I. Priming Effecta. Upregulationb. Downregulationc. Paracrine regulationi. Prostaglandins ii. NSAIDSiii. Isoenzymes Outline of Current Lecture I. Skeletal Muscle a. Myofibersi. A-bandsii. I-bandsb. Mechanism of muscle contractionc. Cross-bridge cycling Current LectureSkeletal Muscle1. Innervated by somatic motor neurons2. Conscious control3. Important in movement and generation of body head4. Figure 12.1a. Lots of connective tissue involvedThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.i. Outer surface: Epimysium – dense layer of connective tissueii. Inside of muscle: Perimysium – divides into units called fasciculiiii. Within one fasciculus, there are multiple muscle cells1. Each cell – muscle fiber, myofiber2. Each surrounded by thin connective tissue called endomysiumiv. Tendon – continuation of epimysium and perimysium after muscle stops –connects to bonev. One connects to origin (stationary) and the other to the insertion (moves)Myofibers1. Very long (can extend centimeters)2. Same diameter as other cells3. Myoblasts arrange in horizontal rows and fuse together (see notes)a. Multinucleateb. Syncytium – fused togetherc. Sarco – fleshi. PM – sarcolemmaii. Cytoplasm – sarcoplasmiii. ER – Sarcoplasmic Reticulumd. Striatedi. Dark red bands – A bandsii. Lighter bands – I bandse. Each myofiber contains structures that look like spaghetti - myofibrilsi. All in centerii. Nucleus shoved to outside along w/ sarcoplasm and SRiii. Myofibrils are composed of subunits called sarcomeresiv. Sarcomeres are in register – they all line upv. See notes for picture of sarcomere1. Composed of myofilaments2. Thin myofilaments – actin, anchored to z disk3. Thick myofilaments – myosin, in center, attached by m-line proteinfibers4. Cross bridges – project out from thick myofilaments5. Region that only contains thick – H zone6. Just thin – I bands7. Thick and thin – A bands8. Titin runs all the way through – largest known protein, acts like a string, returning sarcomeres to resting lengthf. Mechanism of Muscle Contractioni. Sliding filament theoryii. When a muscle contracts, it gets shorter because fasciculi get shorteriii. Fasciculi get shorter because myofibers get shorteriv. Myofibers get shorter because myofibrils get shorterv. Myofibrils get shorter because sacromeres get shortervi. Sarcomeres get shorter because myofilaments slide past each othervii. Cross bridges work like oars attaching to thin myofilaments, pulling toward center of sarcomere1. Asynchronous so titin cannot push thin filament back out2. Z discs get closer together3. I band gets smaller until it disappears4. H zone gets smaller until it disappears5. A band stays the sameviii. Cross Bridge Cycling1. Powered by ATP2. Cross bridge has 2 conformationsa. Phosphorylated – cockedb. Dephosphorylatedc. PHOSPHORYLATION OF CROSS BRIDGE COCKS CROSS BRIDGEd. POWER STROKE RESULT OF DEPHOSPHORYLATIONe. Thick myofilament composed of myosin filamentsf. 1 myosin has a cross bridgeg. cross bridge has an ATPase domain and an actin binding domainh. ATP hydrolyzed to ADP and P, P binds to cross bridge, cocking iti. Break bond – power stroke3. Thin filament composed of f actina. Polymerized from g actinb. Looks like double strand of pearlsc. Has a myosin binding site4. Cross bridge cycle FIGURE 12.12a. Phosphate covalently bonds, cocksb. Attaches to thin myofilamentc. Attachment triggers dephosphorylation of cross bridged. Causes power stroke, which pulls thin myofilament to center of sarcomere and ejects ADPe. ATP binds, causing cross bridge to detach from thin myofilament5. Rigor Mortis – state of a corpse when muscles are all contracted, no ATP is made, and no detachment of cross bridgesg. What prevents cross bridge from attaching?i. Troponin/Tropomyosin complexii. T/TC part of thin myofilamentiii. Tropomyosin is rod shapediv. Troponin complex composed of1. TNT – troponin tropomyosin – attaches to tropomyosin2. TNC – troponin ligand binding site to calcium (presence = contraction)3. TNI – troponin interfering – interferes with cross bridge attachmenta. Tropomyosin blocks myosin binding siteb. TNI move tropomyosin after Ca2+ bindsc. Allows binding to