1. Molecular Structure and Function of Muscle Tissue Nestor T. Hilvano, M.D., M.P.H.

2. Learning Objectives You should be able to: 1. List the major functions of skeletal muscles. 2. Describe the organization of muscle at the tissue level. 3. Discuss how would severing the tendon attached to a muscle affect it’s ability to move a body part. 4. Describe the structural components of a sarcomere. 5. Explain the mechanism of muscle contraction and relaxation. 6. Describe the stages of a muscle twitch and explain how muscle twitches add up to produce stronger muscle contraction. 7. Compare and contrast fast muscle fiber and slow muscle fiber. 8. Distinguish between isometric and isotonic contraction. 9. Explain the basis of muscle fatigue.

3. Introduction to Muscle Movement is fundamental characteristic of skeletal muscle Physiology of skeletal muscle – basis of warm- up, strength, endurance and fatigue Characteristics of muscle – excitability, conductivity, contractility, extensibility, and elasticity Produce movement Functions - Maintain body position, Support soft tissues, Guard openings, Maintain body temperature, Store nutrient reserves

4. Connective Tissue Elements ___ - surrounds the whole (entire) muscle (made up of several fascicles/bundles) ___ - surrounds a bundle (individual fascicle) of muscle cells/fibers ___ - surrounds muscle cell ( each fiber) Tendon (bundle) & aponeurosis (sheet) – attach skeletal muscle to bones a. endomysiumb. perimysium c. epimysium

5. Structure of Muscle Fiber (Cell) ___ - cell membrane of muscle cell ___ - tunnel-like infoldings of sarcolemma ___ - cytoplasm filled with myofibrils (bundles of myofilaments) Muscle striations – alternating dark (A) and light (I) bands ___ - dilated end-sacs of sarcoplasmic reticulum store ___. a. sarcolemma b. sarcoplasm c. T (transverse) tubules d. cisternae e. calcium

6. Myofilaments Myosin (thick, contractile protein) - 2 entwined Polypeptides; long tail and free head (with globular protein) Actin (thin, contractile protein) - Two intertwined strands fibrous (F) actin (with an active site of globular (G) actin) - regulatory proteins: a.) tropomyosin (covers the active site of Actin in relax state) b.) troponin complex (calcium-binding receptor)

7. Sarcomere Sarcomere- structural and functional unit of striated muscles, between the 2 successive Z bands Describe the Mechanism of contraction- “sliding filaments and muscle contraction-cross bridges.”

8. Control of Muscle Activity Neuromuscular junction –functional connection between nerve fiber and muscle cell Components of synapse Pre-synapse- contains Ach Synaptic cleft- tiny gap between nerve and muscle cell Post-synapse- region of sarcolemma increases surface area for ACh receptors contains acetylcholinesterase

9. Correlation Muscles not stimulated by motor neurons on regular basis will atrophy Rigor mortis is a physical state in which muscles lock in contracted position (body stiffness); caused by: - membrane of dead cells are no longer selectively permeable, and calcium leaks in, which triggers contraction - dead muscle cells can no longer make ATP, which is necessary for cross bridge detachment from active sites - begins few hours after death and lasts until approximately 15-25 hours later, when the lysosomal enzymes released by autolysis break down the myofilaments

10. Correlation Twitch = single stimulus-contraction- relaxation sequence Twitch = low frequency (up to 10 stimuli/sec), each stimulus produces an identical response Trappe = moderate frequency (between 10-20 stimuli/sec), has time to recover but develops more tension than the one before (stair- step increase) Wave summation = higher frequency stimulation (20-40 stimuli/ sec), generates gradually more strength of contraction each stimuli arrives before last one recovers (repeated stimulations before the end of relaxation) Tetanus = rapid continuous stimulations and muscle not allowed to relax (40-50 stimuli/second), muscle has no time to relax at all twitches fuse into smooth, prolonged contraction

11. Types of Skeletal Muscle Fibers Fast-twitch fiber = anaerobic, good for strength, larger fibers, lighter color, little or no myoglobin Slow-twitch fiber = aerobic, for endurance, smaller fibers, darker color, contain myoglobin

12. Isometric and Isotonic Contractions Isometric contraction – develops tension without changing length (muscle does not shorten), important in postural muscle function and antagonistic muscle joint stabilization Isotonic contraction a. Isotonic concentric- tension while shortening b. Isotonic eccentric- tension while lengthening ___ holding a dumbbell a. isotonic concentric contraction ___ lifting a dumbbell up b. isotonic eccentric contraction ___ putting down a dumbbell c. isometric contraction

13. Myasthenia Gravis Autoimmune disease - antibodies attack NMJ and bind ACh receptors in clusters –receptors removed –less and less sensitive to ACh drooping eyelids and double vision, difficulty swallowing, weakness of the limbs, respiratory failure Disease of women between 20 and 40 Treated with cholinesterase inhibitors, thymus removal or immunosuppressive agents

14. Homework (Self Review) 1. Define key terms: muscle hypertrophy, muscle atrophy, sarcolemma, sarcoplasm, sarcoplasmic reticulum, neuromuscular junction, troponin, tropomyosin, treppe, tetanus, twitch, atrophy, endomysium, perimysium, epimysium, actin, myosin, synapse, and rigor mortis. 2. Describe the components of sarcomere. 3. Discuss in details the sliding filament theory in muscle contraction (from time of calcium release to changes in actin-myosin filaments cross- bridges). 4. Differentiate isotonic and isometric contraction by citing an example.