Muscle physiology/troponin/tropomysin

1. Electron micrographs reveal bundles of filaments running along the axis of a muscle cell – these bundles are called myofibrils that are in a transverse register across the whole muscle cell; there are dark and light striations within the cell
   1. dark striations are called thick filaments – from the beginning of a thick filament to the end of the thick filament is an A band (Remember A in dArk and ATPase)
      1. thick filaments are formed by myosin; each myosin molecule has two heads attached to the end of a long tail
   2. a second lattice consists of thin filaments that are attached to a transverse, darkly staining structure called the Z line – thin filaments extend from two adjacent Z lines to interdigitate with the thick filaments
      1. thin filaments contain two major proteins: 1) a globular protein actin that forms twisted, two-stranded filaments and 2) a rod shaped tropomyosin
      2. areas containing only thin filaments are called I bands and are light when viewed under polarized light (Remember: I in light and actIn)
      3. the structure from one Z line to another is termed a sarcomere; each sarcomere contains ½ of two I bands and a central A band
      4. the A band (the thick filament) has a less dense central region where there is no overlap in the thin filament called the H zone
         1. the H zone is bisected by a darly staining M line containing proteins that link the thick filaments together
      5. the thin filaments form a hexagonal array around each thick filament while each thin filament is equidistant from three thick filaments
   3. the interaction between actin and myosin, associated with ATP hydrolysis, represents the fundamental chemomechanical transduction process
      1. in resting muscle the thin filament is oriented perpendicularly to the myosin filament
      2. when a muscle is stimulated, a rise in myoplasmic Ca concentration produces changes in the myofilament structure allowing crossbridge binding to the thin filament
         1. in the presence of ATP, myosin has ADP and P bound to each head and has a high affinity for actin
         2. ADP and P are released when the myosin heads bind to actin; product release allows an ATP molecule to bind to myosin and the affinity of myosin for actin is greatly reduced
         3. The bound ATP is hydrolyzed with dissociation of myosin and actin although the products (ADP and Phosphate) remain bound to myosin in the succeeding step
         4. The energy released by splitting of ATP is stored in the myosin molecule which is in a high energy state and has renewed affinity for actin
      3. the hinge regions in the crossbridge permit the head of the myosin to change their tilt using the energy stored in the ADP-Phosphate complex
      4. the conformational change is the crossbirdge generates a force moving the thin filament relative to the thick filament and releases the ADP-P setting the stage for crossbridge detachment when another ATP is bound
      5. each cycle moves the filaments about 10 nanometers relative to each other
      6. cycle continues until interrupted in the detached state by control systems which remove Ca from the myoplasm and produce relaxation or until ATP is exhausted (a rare occurrence)
         1. rigor mortis causes musclular rigidity because ATP depletion leads to permanent crossbridge attachment
   4. in skeletal and cardiac muscles, a regulatory protein called troponin in the thin filament is bound to each end of a tropomyosin molecule; when troponin binds 4 Ca ions the conformation of the thin filament changes; these changes allow crossbridges to form between thick and thin filaments
      1. troponin is not present in smooth muscle and the myosin content of smooth muscle is only ¼ that of striated muscle
   5. skeletal muscle is divided into fast and slow twitch reflecting the firing pattern of the motor neuron; the fast and slow twitch characteristics are not necessarily genetically fixed and thus pathologic conditions affecting the nerve also affect the histochemistry of the muscle fiber
      1. slow twitch (red) fibers have heavy myoglobin and are dark red in color; present in endurance athletes
      2. fast twitch (white) fibers have high glycolytic properties; present in sprinters and weight lifters