BASIM ZWAIN LECTURE NOTES

1. Muscle Thick filaments: Myosin, rodlike tail terminates in two globular heads, tail consistsof heavy meromysin (polypeptide chains (2) interwoven), head consists of ends of heavy meromysin + light meromysin, during contraction heads (cross bridges) interact with thin myofilaments, thin myofilaments: actin, consists of G (globular) actin, double stranded helix regulatory proteins: tropomyosin, sprial around actin, block myosin head binding sites: relaxation, troponin (polypeptide complex), binds Ca2+ (TnC), binds tropomyosin (TnT) & binds actin (TnI) Contraction: potential energy stored in high-energy configuration is used to pivot myosin head (myosin head bends as it pulls on actin, ADP and inorganic phosphate are released from myosin), new ATP attach to myosin head (cross bridge simultaneously detach), following death no ATP (muscle cannot relax: rigor mortis), if no new impulse; Ca2+ is pumped back into (SR), relaxation occurs, if Ca2+ present from additional impulse; cycle repeats (myosin head “steps” to next binding site on actin) Skeletal (striated, voluntary), cardiac (striated, inv-oluntary), smooth (non-striated, involuntary). Common features: elongated cells (fibers), myofila-ments (actin&myosin), comprised of: fibers, CT, blood vessels & nervous tissue. Terminology: myo & sacro. Functions: movement, maintain posture, stabilize joints & temperature homeostasis. Sarcolemma (plasma membrane), sarcoplasm (cyt-oplasm of muscle cells), myofibrils (contractile elements of skm), A-band (dark band): anisotropic (polarize light), I-band (light band): Isotropic(non-polarizing), H-band (within A-band): visible only in relaxed muscle, M-line (bisects H-band), Z-disc (membrane): midline in I-band, Sarcomere (region between two successive Z-discs): functional unit Events during contraction: Nerve impulse (afferent signal) from motor neuron generates AP in nerve cell, AP propagated along sarcolemma and down T tubules, myosin ATPase activated (ATP splits to high energy myosin-ADP complex), AP causes release of Ca2+ from SR, binds to troponin, molecular shape of troponin changes (tropomyosin is removed from binding site of mysosin on the actin filament), myosin attaches to actin. Contraction of skeletal muscle (sliding theory): Thin filaments slide past thick ones, overlap to a greater degree. Prior to contraction cross bridges are disengaged & all bands distinct. Nerve impulse initiates contraction, cross bridges engage, ATP splits, energy used for swinging of cross bridges, actin filaments pulled together, H-zone and Z-disc smaller or lost, I-band reduced, cross bridges disengage & filaments return to original position. Individual fibers surrounded by endomysium (areolar connective tissue), multiple fibers bundled as fascicles, fascicles bound by collagen sheath (perimysium), epimysium surrounds all fascicles, deep fascia binds muscles into functional groups During relaxed state: Ca2+ conc. in sarcoplasm is low (stored in SR), troponin-tropomyosin complex attached to actin filament (to block myosin binding sites on actin filament), ATP and inactive ATPase bound to myosin head (low energy configuration, binding to actin not possible) Microfilaments (myofilaments) with in bands Thick filaments (myosin): entire length of A-band, thin filaments (actin): across I-band & part of A-band, Z-disc (protein sheet connecting myofibrils) Home Exit BASIM ZWAIN LECTURE NOTES

2. Muscle Comparison of skeletal, cardiac & smooth muscle Smooth muscle Motor unit Cardiac Muscle Regulation of Contraction Isotonic and Isometric contractions Tension is force of contracting muscle on an object, load is reciprocal force exerted by object, to move object; tension must be greater than load. Isotonic contraction (change in length): concentric (muscle shortens and does work), eccentric (muscle contracts as it lengthens), concentric and eccentric can occur at the same time, eccentric put muscle to concentric, isometric contraction (tension ncrz but length constant): load greater than force (mainten-ance of posture, most movements involve both Muscle Metabolism ATP is sole source of energy for contraction, little ATP is stored, regenerated (recycled) rapidly: direct phosphorylation of ADP by creatine phosphate, anaerobic glycolysis (in the absence of O2, glycolytic products “pyruvic acid” are metabolized to lactic acid producing additional small quantities of ATP, aerobic respiration: 95% of ATP during light exercise, in presence of O2, products of glycolysis broken down entirely, with generation of large amounts of ATP, glycogen is the source of glucose for both aerobic & anaerobic Transduction events: 1. Nerve impulse, 2. ACh released from presynaptic motor neuron, 3. Binds to receptors, Na+ channels open, depolarizing current, AP, ACh destroyed (ACE), 4. AP propagated, sarcolemma, T tubules, 5. Ca2+ released from SR, 6. Ca2+ removed by Ca2+ pumps, contraction ceases, 7. At individual muscle fibers (cells); contraction is all or nothing, in response to threshold stimuli, APs are generated in a non-graded fashion, 8. Refractory period cells must re-polarize before another AP Red muscles contain higher % of red fibers with few white fibers. They respond slowly, long latency, specialized for posture maintenance, contain more blood capillaries, mitochondria and myoglobin, resistant to fatigue, sensitive to hypoxia. White muscles contain higher % of white fibers, few red fibers, respond quickly, short latency, specialized for fine skilled movements, less blood capillaries, mitochondria and myoglobin, less sensitive to hypoxia, easily fatigued. When nerve to slow fiber replaced by nerve to fast fiber; slow becomes fast! Small, spindle-shaped, sheets of opposing fibers, generally two sheets (longitudinal & circular): peristalsis, lacks highly structured NMJ, lower myosin to actin ratio than skm (1:13 vs. 1:2), lacks troponin complex and sarcomeres. Gap junctions make entire sheet responds to a single stimulus, some has pacemaker, some self-excitatory, Ca2+ interacts with regulatory molecules: calmodulin, slow, sustained & resistant to fatigue. It contracts in response to stretch. Branched, interdigitated, syncytium, intercalated discs, gap junctions, RMP = -85 mV, AP slow, plateau, AP phases are: Phase 0: Depolarization: 2 ms, activation of all Na+ channels, influx of Na+, Phase 1: Initial rapid repolarization, inactivation of Na+ channels, Phase 2: Plateau: 200 ms, opening of Ca2+ channels, influx of Ca2+, Phase 3: Late rapid repolarization, closure of Ca2+ channels, Phase 4: Base line (RMP) Muscle twitch: response of muscle to single supra-threshold stimulus, 3 Phases: latent phase (few ms), contraction phase (10-100 ms), relaxation(10-100 ms) Graded responses depend on stimulation frequency & strength. Temporal (wave) summation: strength of contraction increases with successive stimuli, fibers that are already contracted, contract further with additional Ca2+, if stimulation is delivered prior to relaxation, contractions are summed Tetanus: At high frequencies, no relaxation occurs, contractions fuse, smooth sustained contraction Motor unit summation (response to ncrz stimulus intensity): primary mechanism for ncrz force of contraction, multiple motor unit summation (recruitment), at threshold; first contraction, as stimulus intensity ncrz; additional units activated, maximal stimulus: strongest, causes ncrz contract-ion, accomplished by ncrz neural activation Synapseis site of communication between neuron and muscle (neuron to neuron in nervous system): Contact is not direct, physical separation, synaptic cleft, requires signal, transduced to chemical signal (NT, ACh is NT at NMJ) Motor end plate is physical modification of sarco-lemma where neuron synapses with fiber, ACh receptors located on motor end plate Could be small in size (few collaterals arise from motor nerve to supply few muscle fibers) or large in size (so numerous collaterals and muscle fibers). Three types of muscle fibers: Slow oxidative fibers (slow red), fast oxidative fibers (fast red) which is very rare in human, fast glycolytic fibers (fast white). Skeletal muscle is a mixture of these types of fibers, so there are red and white muscles Property of stress-relaxation (plasticity) , gradual increase in stretch; tension increase then decrease even below its initial level, uterus to adapt increase in fetal size, urinary bladder to adapt increase in urine volume. Sm in continuous partial contraction (tone), nerve supply & multiple NT to modify tone, also affected by chemicals, pH, temperature, CO2, O2 ....etc, Two types of sm: Single-unit & Multi-unit Pacemaker potential: Cardiac muscle contraction myogenic, (originated in muscle) not neurogenic (initiated by nerve), nerve is regulatory: presence of specialized conductive tissue in heart, pacemaker tissue, unstable low potential, prepotential, declines & depolarizes continuously: decrease in K+ efflux, spreads impulses all over heart. Steeper prepotent-ials: tachycardia, lower prepotentials: bradycardia. Single-unit smooth muscle: Function as syncytium, found mainly in the wall of hollow viscera. Multi-unit smooth muscle: No gap junctions, each muscle works individually, found in the iris of eye, vas deferens, epididymus, large pulmonary airways and large blood vessels. They have many functional similarities to skeletal muscles but irregularly and involuntarily contract with prolonged duration. Neuromuscular junctionisconnection between somatic nervous system and muscles: motor neuron axons bifurcate to form multiple endings: separate endings synapse with individual mfs (mf synapses with single motor neuron, motor neurons synapse with multiple mf) Treppe force of contraction ncrz during response to stimuli at the same strength, result of ncrz Ca2+ availability, heat created during contraction ncrz efficiency of enzymes (warming, athletic activity) Velocity and duration of contraction l as load ncrz, velocity and duration decrease, muscle fiber type (slow or fast), pathway for ATP formation (aerobic or anaerobic glycolysis) Force of Contraction more motor units recruited; greater force, greater cross sectional area; greater tension, optimum resting length is the length at which maximum force can be generated Fatty acids are the major source of energy at rest Home Exit BASIM ZWAIN LECTURE NOTES

3. Muscle Muscle Mechanics Home Exit BASIM ZWAIN LECTURE NOTES