The Muscular System Muscles are the “the machines of the body” Contraction “shortening” – unique characteristic that sets muscle tissue apart from other tissue Overview of Muscle Tissue All muscles … Are elongated (muscle fibers) Contraction depends on microfilaments Latin prefix ‘myo’ and ‘mys’ - muscle ‘sarco’ - flesh Muscle Tissue Characteristics • Excitability (irritability) – response (electrical impulse) to stimuli (usually chemical) producing contraction • Contractility – shorten forcibly • Extensibility – able to be stretched • Elasticity –resume resting length Classification of Muscle Types -Skeletal -Cardiac -Smooth I. Skeletal Muscle 1. Cover skeleton – attaching to bone, muscle and/or skin 2. Cell shape - single, very long, cylindrical, multinucleate, striated 3. Voluntary – (via nervous system) 4. Can contract rapidly but tires easily 5. Fragile – layered strength Classification of Muscle Types II. Smooth Muscle 1. Found in walls of hollow visceral organs 2. Cell shape – single, fusiform, uninucleate, no striations 3. Involuntary – controlled by nervous system, hormones, chemicals, response to stretch 4. Very slow contraction Classification of Muscle Types III. Cardiac Muscle 1. Found in walls of the heart 2. Cell shape – branching chains of cells, uninucleate, striations 3. Involuntary 4. Slow contraction (rhythmic) Muscle Functions 1. 2. 3. 4. Produce movement Maintain posture Stabilize joints Generate heat – Muscle = group of fascicles – Muscle fibers extend length of muscle from tendon to tendon Skeletal Muscle – Gross Anatomy • Muscle (organ) – muscle fibers, blood vessels, nerve fibers and connective tissue (CT) • Each muscle served by one nerve, an artery, one or more veins, CT sheaths • Organization (large to small) Muscle (organ)→ Fascicle (muscle portion)→ Muscle fiber (cell) → Myofibril (organelle with bundles of myofilaments) →Sarcomere (myofibril segment) → Myofilament (thick and thin) Skeletal Muscle – Gross Anatomy • Connective Tissue Sheaths Individual muscle fibers wrapped and held together by CT sheaths (Internal → External) Endomysium [reticular fibers]– surrounds each muscle fiber → Muscle fibers grouped into Fascicles (bundles) and surrounded by Perimysium [fibrous CT]→Epimysium [dense irregular CT] which surrounds the whole muscle Components of a muscle fiber Skeletal Muscle – Gross Anatomy • Connective Tissue Sheaths Sheaths are continuous with one another and with tendons During contraction, muscle fibers pull on sheaths which transmit force to bone to be moved Contribute to muscle elasticity Entry and exit for blood vessels and nerves Muscle fiber components • Sarcolemma: muscle cell membrane • Sarcoplasma: muscle cell cytoplasm • Motor end plate: contact surface with axon terminal • T tubule: cell membrane extension into the sarcoplasm (to reach the myofibrils) • Cisternae: areas of the ER dedicated to Ca++ storage (located on each side of the T-tubules) • Myofibrils: organized into sarcomeres Figure 12.2 (2 of 2) Attachments • Skeletal muscle spans joints and attaches to bones in two places – When a muscle contracts, the movable bone (muscle’s insertion) moves toward the less movable bone (muscle’s origin) – In limbs, origin lies proximal to insertion • Direct Attachments – epimysium fuses to periosteum (bone) or perichondrium (cartilage) • Indirect – Muscle’s CT wrappings extend beyond muscle as ropelike tendon or sheet-like aponeurosis – Connects to CT (bone/cartilage) or fascia (muscle) Skeletal Microscopic Anatomy Sarcolemma … Layer underneath plasma membrane Myofibril … long, ribbon-like organelles which nearly fill cytoplasm; bundles of myofilaments Striations Light (I) Bands and Dark (A) Bands create Banding Pattern Skeletal Microscopic Anatomy I band … light A band …dark Z line … darkened midline interruption H zone … lighter central region which interrupts A band Sarcomere … tiny contractile units of myofibril Myofilaments … threadlike proteins Skeletal Microscopic Anatomy Myofilaments are made up of the protein molecules Myosin –make up “thick” filaments Actin – make “thin” filaments Myosin has rodlike tail and globular heads Heads link thick to thin filaments (cross bridges) during contraction Arrangement of myofilaments determine banding pattern The sarcomere • The myofibrils are organized into a repetitive pattern, the sarcomere • Myosin: thick filament • Actin: thin filament • Bands formed by pattern: A and I and H bands • Z line: area of attachment of the actin fibers • M line: Myosin fiber centers The sarcomere Figure 12.5d Myosin structure • Many myosin molecules per filament, golf club shape • Long tail topped by a thickening: the head forms crossbridges with the thin filament • Presence of the enzyme, ATPase in the head release energy for contraction Actin structure • Formed by 3 different proteins: - globular (G) actins: bind to myosin heads - tropomyosin: long, fibrous molecule, extending over actin, and preventing interaction between actin and myosin - troponin: binds reversibly to calcium and able to move tropomyosin away from the actin active site Figure 12.4 Contraction of Skeletal Muscle • “All or None” Law of Muscle – applies to single muscle cell • Skeletal Muscle – organ of thousands of muscle cells – Graded Responses • Different degrees of shortening – Produced by changing speed and changing # cells Skeletal Muscle Activity • Muscle Cells … special functional properties – Irritability – ability to receive and respond to stimulus – Contractility – ability to shorten when an adequate stimulus is received Action Potential • Motor neuron may stimulate more than 1 muscle • Motor Unit - motor neuron and all muscle fibers it supplies – Fine control muscles –small motor units – Large weight-bearing muscles – large motor units Muscle contraction is investigated in lab using an apparatus producing a myogram (recording of contractile activity); line recording is a tracing. Motor units • Motor unit: Composed of one motor neuron and all the muscle fibers that it innervates • There are many motor units in a muscle • The number of fibers innervated by a single motor neuron varies (from a few to thousand) • The fewer the number of fibers per neuron the finer the movement (more brain power) Action Potential • To contract, a skeletal muscle fiber must be stimulated by a nerve and propagate an electric current (action potential) along its sarcolemma – Action potential causes a short-lived rise in intracellular Ca2+ levels – triggers contraction – Axon (nerve fiber)… long threadlike extension of neuron • Axonal Terminals… branches of axon which forms junction with muscle (Neuromuscular Junctions) – Separating space – Synaptic Cleft Action Potential • Action Potential … “unstoppable” – Within axonal ending are synaptic vesicles containing acetylcholine (ACh) – Motor end plate of sarcolemma has ACh receptors – Nerve impulse causes Ca2+ to flow into axon from extracellular fluid and release ACh into synaptic cleft – ACh fuses onto sarcolemma receptors resulting in change in membrane potential – Breakdown of ACh prevents continued contraction Synaptic events • The AP reaches the axonal bulb • Voltage-gated calcium channels open • The influx of calcium in the bulb activates enzymes the vesicles containing the neurotransmitter molecule dock and release the neurotransmitter in the synapse • The neurotransmitter for skeletal muscles is always acetylcholine • The receptors on the muscle fiber are cholinergic receptors • These receptors are nicotinic (fast) acting receptors 2- The Mechanism of Force Generation in Muscle Figure 12.7 Muscle relaxation • Ach is removed from the receptors by acetylcholinesterase • Ligand-gated Na+channels close • Na/K pumps reestablish the RMP • Ca++ ions leave troponin and are brought back into the cisternae (this process needs energy) • Tropomyosin moves back over the actin active site • The myosin heads release their binding to actin • The filaments passively move back into resting position Applications • Myasthenia gravis: autoimmune disease where antibodies against the Ach receptors are produced. Which consequences do you expect? • Muscular dystrophy: some proteins forming the muscle fibers are abnormal. Which consequences do you expect? • Curare binds to the Ach receptor without activating them. What are the effect of curare on the skeletal muscle? • The botulism toxin prevents the release of the neurotransmitter into the synapse. What will be the consequence? • Nerve gas inhibits acetylcholinerestase present in the synapse. What will be the consequence? • • Rigor mortis: why does the body stiffen shortly after death? Sliding Filament Theory This theory of contraction states that during contraction the thin filaments slide past the thick ones so that the actin and myosin filaments overlap to a greater degree – ATP – Each cross bridge attaches/detaches several times during contraction – Muscle cell shortens – Attachment of myosin to actin requires Ca2+ (from sarcoplasmic reticulum) – Single nerve impulse produces 1 contraction – prevents continuous contraction Contraction of Skeletal Muscle • Tetanus …goal: to produce smooth and prolonged muscle contraction – Strength correlates to # cells – Strongest contraction – when all motor units are active and stimulated – Muscle twitch…single, brief, jerky contractions – Graded muscle responses (response to varying demands): contractions graded • By changing the frequency of stimulation • By changing the strength of the stimulus Energy For Muscle Contraction • As muscle contracts, ATP hydrolysed to release energy – Only energy source – Continuous supply: – Regeneration of ATP (3 ways) • Direct phosphorylation of ADP by creatine phosphate (CP) –muscles store more CP than ATP CP → creatine while ADP → ATP (Coupled Reaction) [ADP +CP → ATP + creatine] Efficient & Quick Energy For Muscle Contraction • Aerobic Respiration – Takes place in mitochondria – During exercise, ATP generated by processes that use O2 [C6H12O6 + 6O2 → 6CO2 + 6H2O + ATP] – High yield of ATP (36 per 1 glucose) – Slow because of steps – Requires continuous supply O2 Energy For Muscle Contraction • Anaerobic Glycolysis – ATP generated by processes that do NOT require O2 – Glucose converted to pyruvic acid releasing ATP (2 ATP per 1 glucose) – If O2 supplied, pyruvic acid undergoes aerobic respiration (mitochondria) to produce CO2 and H2O + 36 ATP – When muscle activity reaches 70% of maximum, O2 is not supplied (muscles bulge) and pyruvic acid converts to lactic acid Energy For Muscle Contraction • Anaerobic Glycolysis (continued) – Glucose → Pyruvic acid → Lactic acid – Fast (2.5 times faster than aerobic) – Less ATP produced (5% of aerobic) – Accumulating lactic acid results in muscle fatigue and soreness Muscle Fatigue/Oxygen Debt • Strenuous exercise results in muscle fatigue (muscle unable to contract) • Muscle fatigue caused by oxygen debt (prolonged muscle activity) – Cannot take in oxygen fast enough to keep muscles supplied – Lactic acid increase True muscle fatigue – muscle quits entirely Contractures – no ATP available for cross bridges to detach (continuous contraction) – writer’s cramp (temporary); rigor mortis (permanent) Muscle Fatigue/Oxygen Debt • Example: If running 100-yard dash in 12 seconds requires 6L O2 for complete aerobic respiration, but VO2 max of muscles is 1.2L for that 12 seconds, then there is an oxygen deficit of 4.8L – – – – Oxygen Debt must be “paid back” Repay by breathing deeply (triggered by high H+ in blood) Rid of lactic acid Rise in ATP Muscle Contractions • When muscle contracts, Tension (force) develops as actin and myosin slide and interact – Isotonic contraction – “same tone” myofilaments successfully slide, muscle shortens, movement occurs – Isometric contraction – “same measure” muscle does not shorten, tension increases, myofilaments skid (usually when trying to move something immovable) IV- Muscle metabolism • Muscle fibers use ATP (only first few seconds) for contraction • ATP must then be generated by the muscle cell: - from creatine phosphate, first - from glucose and glycogen - from fatty-acids ATP formation from the above compound is possible if oxygen is present (oxidative phosphorylation) Oxygen is delivered to the muscle by myoglobin, a molecule with high affinity to oxygen and related to hemoglobin If the effort is strong and sustained, the muscle might not have enough oxygen delivered to it by myoglobin anaerobic glycolysis with only 2 ATP formed per glucose and synthesis of lactic acid Figure 12.11 Muscle fatigue • Muscle fatigue: a decline in the ability of the muscle to sustain the strength of contraction • Causes: - rapid build-up of lactic acid - decrease in oxygen supply - decrease in energy supply (glucose, glycogen, fatty-acids) - Decreased neurotransmitter at the synapse - psychological causes Muscle Tone • State of continuous partial contraction • Keeps the muscles firm, healthy and ready to respond • Skeletal muscle tone helps stabilize joints and maintain posture • Nerve damage → can’t stimulate muscle → reduce tone → flaccid (soft/flabby) → atrophy Golden Rules of Skeletal Muscle Activity • All muscles cross at least 1 joint • The bulk of the muscle lies proximal to the joint crossed • All muscles have at least 2 attachments (origin & insertion) • Muscles can only pull, they never push • During contraction, the muscle insertion moves toward the origin Force of Muscle Contraction • Force of contraction is affected by – Number of muscle fibers stimulated • More motor units, more force – Size of muscle fibers stimulated • Bulkier the muscle, more tension (greater strength) – Frequency of stimulation • Internal tension (force generated by myofibrils) transfer tension (external tension) to load – Degree of muscle stretch – severely stretched (or severely contracted ) muscle can’t develop tension (improper overlap of filaments) Muscle Fiber Type • Speed of Contraction - how fast myosin ATPases split ATP – Slow fibers – Fast fibers • Major pathways for forming ATP – Oxidative fibers (aerobic) – Glycolytic fibers (anaerobic) Skeletal muscle cells are slow oxidative fibers; fast oxidative fibers; or fast glycolytic fibers. Smooth Muscle • Microscopic Structures – Spindle-shaped, one centrally located nucleus, narrower and shorter than skeletal muscle cells, lack coarse CT sheaths, no striations, no sarcomeres – Organized into sheets of closely apposed fibers • Longitudinal layer: fibers run parallel to long axis of organ (Contracts- organ dilates and shortens) • Circular layer: fibers run around the circumference of organ (Contracts- constricts the lumen (cavity) of organ and cause elongation) – Alternating contraction/relaxation - peristalsis Contraction of Smooth Muscle • Adjacent muscle fibers exhibit slow, synchronized contractions • Whole sheet responds in unison • Electrical coupling by gap junctions – Transmit action potentials from fiber to fiber • Pacemaker cells set contractile pace for entire sheet • Rate and intensity of contraction may be modified by neural and chemical stimuli Contraction of Smooth Muscle • Takes 30 times longer to contract and relax than skeletal muscle • Can maintain same contractile tension for prolonged period at 1% of energy cost – Sluggishness of ATPases; myofilaments may latch together during prolonged contractions – Important for homeostasis: smooth muscle tone (day in and day out without fatigue) – Low energy requirements Contraction of Smooth Muscle • Stress-relaxation response – Allows hollow organ to fill or expand slowly to accommodate greater volume without promoting contractions (bladder) • Length and Tension changes – Stretches more and generates more tension than comparably stretched skeletal muscle (stretch but not get flabby) • Hyperplasia (divide to increase numbers) –uterus during pregnancy Types of Smooth Muscle • Muscle in different organs varies in fiber arrangement, responsiveness, and innervation – Single-unit (visceral muscle) • • • • • Contract rhythmically and as a unit Coupled by gap junctions Exhibit spontaneous action potentials Arranged in opposing sheets Exhibit stress-relaxation reponse Types of Smooth Muscle • Multiunit – smooth muscles in large airways, large arteries, arrector pili, and internal eye muscles – Gap junctions are rare, infrequent spontaneous synchronous depolarizations – Like skeletal muscles – multiunit fibers are independent of each other – Richly supplied with nerve endings (motor unit) – Responds with graded contractions – Innervated by autonomic system – Responsive to hormonal controls