Biology 325 Fall 2004 Muscle physiology I Introduction A Muscle types 1 Skeletal muscle 2 Smooth muscle 3 Cardiac muscle B Functional characteristics of muscle 1 Excitability irritability 2 Contractility 3 Extensibility 4 Elasticity II Skeletal muscle A Gross anatomy muscles as organs 1 Connective tissue coverings loose areolar connective tissue sheath surrounding each individual muscle fiber cell endomysium several ensheathed muscle fibers grouped into fascicle by collagenic sheath perimysium several fascicles together with blood vessels and nerves wrapped by a fibrous connective tissue layer epimysium all these three CT sheaths are continuous with one another and often extend beyond the muscle itself forming a tendon or aponeurosis 2 Muscle is richly vascularized has extensive innervation each individual muscle fiber is innervated by an axon terminal of a motor neuron capillaries wrap themselves around individual muscle fibers 3 Attachments muscles attached to bone at origin or insertion attachments can be direct epimysium periosteum fusion or indirect through tendons B Microscopic anatomy of a muscle fiber the reductionist ladder general characteristics long cylindrical multinucleate sarcolemma with a system of invaginations well developed endoplasmic sarcoplasmic reticulum however most visible structures are the myofibrils 1 Myofibrils rod like run length of cell contractile elements of muscle fiber composed of an orderly repetitive arrangement of thick and thin filaments myofilaments that gives skeletal muscle its characteristic striated pattern point where adjacent thin filaments attach to one another Z line the area of myofibril between two adjacent Z lines sarcomere the basic structural functional unit of skeletal muscle the contractile unit of skeletal muscle the I band is a light band area of only thin filaments bisected by Z line thus I band involves two adjacent sarcomeres the A band a dark band is an area that contains both thick and thin filaments the H zone is a lighter area in the center of the A band its is a central area that contains only thick filaments as opposed to the rest of A band that contains both thick and thin filaments M line is a dense line that bisects the H zone represents a more dense part of the thick filaments 2 Ultrastructure molecular composition of myofilaments a Thick filaments made up of myosin myosin molecule has long tail two globular heads molecule made up of two heavy chains and four light chains the light chains and the Nterminal portions of the heavy chains combine to form the globular heads the shaft comprised of intertwined area of the heavy chains N terminus of each heavy chain contains an ATP binding site and an actin binding site high energy conformation vs low energy conformation cocked head vs uncocked head each thick filament made up of several hundred myosin molecules the tails forming the core of the filament and the globular heads cross bridges facing outward b Thin filaments composed of actin tropomyosin troponin complex i actin individual actin molecule is a globular protein G actin has ATP binding site binding of ATP by G actin leads to polymerization the ATP is hydrolyzed but ADP held in the actin filaments G actin monomers polymerize to form a two stranded helix F actin a molecule of F actin forms the core of the thin filament and the F actin filament has sites on each subunit that can bind myosin high affinity for myosin heavy chain ii actin binding proteins tropomyosin and troponins each F actin strand associated with two molecules of tropomyosin and several molecules of troponin tropomyosin a fibrous protein long polypeptide chain building blocks are dimers tropomyosin chains cover the myosin binding sites on the F actin strand troponins a complex of globular proteins attached to both the actin and tropomyosin molecules TnI is inhibitory troponin and binds actin TnT binds tropomyosin TnC binds calcium ions if they are around thus in resting state TnC has no Ca bound to it the tropomyosin molecules cover the myosin binding sites on the F actin strand when cell is stimulated intracellular Ca increases dramatically binds TnC this changes conformation of Tn complex which in turn causes the tropomyosin chains to slide into the groove between F actin strands uncovering the myosin binding sites on the Factin strands 3 Sarcotubular system myofibers have two sets of intracellular tubules that participate in the regulation of muscle cell contraction a transverse or T tubules invaginations of the sarcolemma winding holes through the cell bring outside of the cell to the proximity of the contractile machinery of cell lumen continuous with extracellular space transverse cell at A I band junction b longitudinal tubules or L tubules the cell s sarcoplasmic reticulum portions of Ltubule system of special interest are the terminal cisternae these are expanded areas of the sarcoplasmic reticulum located at the junction of A I bands have ability to sequester Ca triad complex of two terminal cisternae and a T tubule C Contraction of a skeletal muscle fiber 1 The sliding filament theory of muscle contraction Huxley and Huxley 1954 when a muscle contracts the individual sarcomeres shorten hence myofibrils also shorten however none of the myofilaments change length thin filaments simply slide past the thick filaments so that they overlap to a greater degree H zone disappears I bands shorten A bands do not change length move closer together sliding of filaments caused by a series of attachment detachment cycles of myosin heads on actin binding sites myosin heads crawl along actin filament recall that in the resting state TnC has no Ca bound to it the tropomyosin molecules cover the myosin binding sites on the F actin strand when cell is stimulated intracellular Ca increases dramatically binds TnC this changes conformation of Tn complex which in turn causes the tropomyosin chains to slide into the groove between F actin strands uncovering the myosin binding sites on the F actin strands myosin head in high energy conformation ADP and Pi bound to it is strongly attracted to exposed binding sites on actin and crossbridge binding quickly occurs this results in a conformational change in the myosin head the head swivels pulling on the actin filament sliding past it the power stroke as myosin head swivels ADP Pi released exposing ATP binding site on the myosin head ATP binding to head causes a conformational change in the head and the