Cellular Basis of Muscle Contraction Claudia Stanescu Ph D Office Hours in Gittings 108 Tue 10 11am and Thurs 1 2pm or by appointment Objectives 1 Diagram and label the thin and thick filaments including all of the proteins that make up each myofilament 2 Give a general description of the sliding filament mechanism 3 Describe the contraction cycle 4 Describe rigor mortis Structural Organization of Skeletal Muscle muscle muscle fiber myofibril sarcomere Sarcomeres Functional Unit of Contraction Elements of Sarcomere Structure Z 1 Thin Filament Attached to Z line Z disc actin troponin tropomyosin determine when contraction occures actin has region brown dot myosin binding site tropomyosin covers binding sites troponin controls tropomyosin troponin Ca shifts tropomyosin begins contraction two twisted strands of pearls composed of two helically arranged strands of actin myosin binding site on actin covered by regulatory proteins Sarcomeres Functional Unit of Contraction Elements of Sarcomere Structure 2 Thick Filament Z highly organized 3D structure 6 thin around each thick myosin heads stick out for interaction with thin all 6 spans the distance and overlaps thin filaments imagine two golf clubs with their handles twisted about each other head interacts cross bridges generates force energy from ATP composed of a highly organized array of myosin molecules myosin head has ATPase actin and myosin interaction activity when bound to actin ATPase enzyme which breaks down ATP energy to change position of myosin head in contraction structural helps w relaxation Contractile Proteins 1 Actin found in thin filaments has myosin binding sites for crossbridge formation with myosin 2 Myosin found in thick filaments has myosin head that binds to the myosin binding site on actin and forms crossbridge during muscle contraction ATPase activity during cross bridge cycling Regulatory Proteins 1 Tropomyosin found in thin filaments covers the myosin binding sites on actin when muscle is relaxed 2 Troponin where Ca binds causes confirmational shape change which shifts tropomyosin which exposes binding sites Found in thin filaments Holds tropomyosin in place when muscle is relaxed During contraction calcium binds to troponin and causes a conformational change that shifts tropomyosin away from the myosin binding sites on actin exposes the binding sites to allow crossbridge formation Sliding Filament Model of Muscle Contraction 1 Myosin heads bind to actin to form a crossbridge 2 Conformational change energized by ATP hydrolysis causes thin filaments to slide along thick filaments stay in place grab thin and pull into sarcomere 3 Myosin head groups release form new crossbridges and the sliding cycle repeats as long as Ca and ATP around Result Z lines move toward one another Sarcomere length decreases Myofibril shortens Muscle fiber shortens As Thick Thin filament overlap increases I band length decreases A band length remains constant H zone length decreases Zone of overlap increases only one that increases shortens sarcomere myrofibril muscle fiber I band almost disapears Davidson College Biology 111 Home Page http www bio davidson edu misc movies musclcp mov Muscle contraction animation Cross Bridge Cycle animation captioned http www youtube com watch v Tuzr5N0T InM Crossbridge Cycling Cycle is entered following exposure of myosin binding sites on the actin thin filament regulatory role for Ca2 starts when Ca is available in muscle in order to have Ca there electrical signal must happen in brain Prior to entering the contraction cycle at the end of the inside of muscle fiber with intercellular fluid last muscle contraction floods once done contracting resetting of myosin heads happens to prepare for next contraction 1 ATP binds to the myosin head at end of contraction 2 This ATP is hydrolyzed by the unbound head and the released energy results in a conformational down into ADP and phosphate cocking of the head group broken leads to conformational position ready to bind the ADP and Pi remain bound to the cocked head adp and phosphate bound to head at end of each contraction http www bms ed ac uk Crossbridge Cycling myosin head actin The contraction cycle begins when Ca2 is released from the SR binds to troponin and the myosin binding sites on actin are exposed m line happens repeatedly as long as ATP present 4 causes head to change position so it can bind again z disc whole process reversible 1 Starting point muscle is ready to contract because myosin heads are cocked and binding sites are exposed 3 2 energy released from phosphate bond moves head back to cocked position rigor complex imagine like an arm moving filament above Contraction cycle steps at rest head in cocked position ready to bind 1 Myosin binding sites on actin become exposed when Ca2 binds to troponin 2 Myosin heads bind to actin forming crossbridges 3 Myosin heads pivot toward the center of the sarcomere power stroke 4 ATP binds to the myosin head detachment of myosin head from actin crossbridges break 5 ATP is hydrolyzed and the energy released is used to re energize the myosin head back to its start position cocked so a new crossbridge can form 6 The contraction cycle repeats until the myosin binding sites on actin are no longer available Rigor complex like rigor mortis rigor of death The attached head group after the power stroke is called a rigor complex Rigor mortis the rigor of death because of lack of ATP to detach the crossbridge 2 Ca leaks out of membranes and causes head to attach and power stroke and then they get stuck because ATP doesn t happen to detach cross bridge stays contracted 4 hours after death up to 24 hours can cause movement in dead people ATP is needed to detach the cross bridge 3 2 San Diego State University College of Sciences Biology 590 Human Physiology Actin Myosin Crossbridge 3D Animation http www sci sdsu edu movies actin myosin html