Neuromuscular A&P Special lecture powerpoint assembled by T.A. Trendler for her wonderful PHYSO 2A class in Fall 2008 From Saladin’s A&P Chapters 5, 11 & 12* Given November 10 & 12 Overview • Given only 2 days to cover 2 really important chapters • I decided to integrate the main topics powerpoint • We’ll cover the anatomy on Monday • Then the physiology on Wednesday • Okay? MyOLOGy Myology: study of muscular tissues (Chapter 5 in Saladin) Myo: latin for muscle (mus = mouse, -cle = little) Sarco: greek for flesh/body (think sarcophagus, body box) Muscle tissue characteristics: excitable, conductive, contractile & extensible* *elasticity due to connective tissues Functions: Motion of body parts (or substances in body) Stability of body parts (or substances in body) Heat production (basal metabolic rate & shivering) Types of Muscle Tissue Skeletal* muscle tissue striated & voluntary studied as the muscular system Cardiac muscle tissue striated & autorhythmic Smooth muscle tissue nonstriated & involuntary Skeletal Muscle • Long, cylindrical, unbranched cells with striations and multiple peripheral nuclei • movement, facial expression, posture, breathing, speech, swallowing and excretion 5-5 Muscular Dystrophy • Hereditary diseases - skeletal muscles degenerate and are replaced with adipose • Disease of males • appears as child begins to walk • rarely live past 20 years of age • Dystrophin links actin filaments to cell membrane • leads to torn cell membranes and necrosis • Fascioscapulohumeral MD -- facial and shoulder muscle only 11-6 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 11-7 Myasthenia Gravis Drooping eyelids and weakness of muscles of eye movement 11-8 Cardiac Muscle • Short branched cells with striations and intercalated discs • one central nuclei per cell • Pumping of blood by cardiac (heart) muscle 5-9 Cardiac Muscle 1 • Thick cells shaped like a log with uneven, notched ends • Linked to each other at intercalated discs • electrical gap junctions allow cells to stimulate their neighbors • mechanical junctions keep the cells from pulling apart • Sarcoplasmic reticulum less developed but large T tubules admit Ca+2 from extracellular fluid • Damaged cells repaired by fibrosis, not mitosis 11-10 Cardiac Muscle 2 • Autorhythmic due to pacemaker cells • Uses aerobic respiration almost exclusively • large mitochondria make it resistant to fatigue • very vulnerable to interruptions in oxygen supply 11-11 Smooth Muscle • Short fusiform cells; nonstriated with only one central nucleus • sheets of muscle in viscera; iris; hair follicles and sphincters • swallowing, GI tract functions, labor contractions, control of airflow, erection of hairs and control of pupil 5-12 Smooth Muscle • Fusiform cells with one nucleus • 30 to 200 microns long and 5 to 10 microns wide • no striations, sarcomeres or Z discs • thin filaments attach to dense bodies scattered throughout sarcoplasm and on sarcolemma • SR is scanty and has no T tubules • calcium for contraction comes from extracellular fluid • If present, nerve supply is autonomic • releases either ACh or norepinephrine 11-13 Types of Smooth Muscle • Multiunit smooth muscle • largest arteries, iris, pulmonary air passages, arrector pili muscles • terminal nerve branches synapse on myocytes • independent contraction 11-14 Types of Smooth Muscle • Single-unit smooth muscle • most blood vessels and viscera as circular and longitudinal muscle layers • electrically coupled by gap junctions • large number of cells contract as a unit 11-15 Stimulation of Smooth Muscle 11-16 Stimulation of Smooth Muscle • Involuntary and contracts without nerve stimulation • hormones, CO2, low pH, stretch, O2 deficiency • pacemaker cells in GI tract are autorhythmic • Autonomic nerve fibers have beadlike swellings called varicosities containing synaptic vesicles • stimulates multiple myocytes at diffuse junctions 11-17 Features of Contraction and Relaxation • Calcium triggering contraction is extracellular • calcium channels triggered to open by voltage, hormones, neurotransmitters or cell stretching • calcium ions bind to calmodulin • activates light-chain myokinase which activates myosin ATPase • power stroke occurs when ATP hydrolyzed • Thin filaments pull on intermediate filaments attached to dense bodies on the plasma membrane • shortens the entire cell in a twisting fashion 11-18 Features of Contraction and Relaxation • Contraction and relaxation very slow in comparison • slow myosin ATPase enzyme and slow pumps that remove Ca+2 • Uses 10-300 times less ATP to maintain the same tension • latch-bridge mechanism maintains tetanus (muscle tone) • keeps arteries in state of partial contraction (vasomotor tone) 11-19 Contraction of Smooth Muscle 11-20 Responses to Stretch • Stretch opens mechanically-gated calcium channels causing muscle response • food entering the esophagus brings on peristalsis • Stress-relaxation response necessary for hollow organs that gradually fill (urinary bladder) • when stretched, tissue briefly contracts then relaxes • Must contract forcefully when greatly stretched • thick filaments have heads along their entire length • no orderly filament arrangement -- no Z discs • Plasticity is ability to adjust tension to degree of stretch such as empty bladder is not flabby 11-21 “Gross” Muscle Anatomy Skeletal muscles are organs Muscle cells are called “fibers” (myofibers) Nervous tissue -> sensory & motor neurons Blood vessels (lined by epithelia) Connective tissue wrappers endomysium, perimysium, epimysium, fascia, tendons vs. aponeuroses collagen is extensible and elastic* A Myofiber MYOFiber specializations Multiple flattened nuclei just inside cell membrane • fusion of multiple myoblasts during development satellite cells nearby can multipy/produce some new myofibers Sarcolemma with transverse (T) tubules that penetrate the cell • carry electric current to cell interior Sarcoplasm is filled with • myofibrils (bundles of myofilaments) • glycogen for stored energy and myoglobin for binding oxygen Sarcoplasmic reticulum = smooth ER • network around each myofibril • dilated end-sacs (terminal cisternae) store calcium • triad = T tubule and 2 terminal cisternea 11-27 Thick Filaments • Made of 200 to 500 myosin molecules • 2 entwined polypeptides (golf clubs) • Arranged in a bundle with heads directed outward in a spiral array around the bundled tails • central area is a bare zone with no heads 11-28 Thin Filaments • Two intertwined strands fibrous (F) actin • globular (G) actin with an active site • Groove holds tropomyosin molecules • each blocking 6 or 7 active sites of G actins • One small, calcium-binding troponin molecule on each tropomyosin molecule 11-29 Elastic Filaments • Springy proteins called titin • Anchor each thick filament to Z disc • Prevents overstretching of sarcomere 11-30 Regulatory vs. Contractile Proteins • Myosin and actin are contractile proteins • Tropomyosin and troponin = regulatory proteins • switch that starts and stops shortening of muscle cell • contraction activated by release of calcium into sarcoplasm and its binding to troponin, 11-31 • troponin moves tropomyosin off the actin active sites Overlap of Thick and Thin Filaments 11-32 Striations = Organization of Filaments • Dark A bands (regions) alternating with lighter I bands (regions) • anisotrophic (A) and isotropic (I) stand for the way these regions affect polarized light • A band is thick filament region • lighter, central H band area contains no thin filaments • I band is thin filament region • bisected by Z disc protein called connectin, anchoring elastic and thin filaments • from one Z disc (Z line) to the next is a sarcomere 11-33 Striations and Sarcomeres 11-34 Relaxed and Contracted Sarcomeres • Muscle cells shorten because their individual sarcomeres shorten • pulling Z discs closer together • pulls on sarcolemma • Notice neither thick nor thin filaments change length during shortening • Their overlap changes as sarcomeres shorten 11-35 Nerve-Muscle Relationships • Skeletal muscle must be stimulated by a nerve or it will not contract • Cell bodies of somatic motor neurons in brainstem or spinal cord • Axons of somatic motor neurons = somatic motor fibers • terminal branches supply one muscle fiber • Each motor neuron and all the muscle fibers it innervates = motor unit 11-36 Motor Units • A motor neuron and the muscle fibers it innervates • dispersed throughout the muscle • when contract together causes weak contraction over wide area • provides ability to sustain long-term contraction as motor units take turns resting (postural control) • Fine control • small motor units contain as few as 20 muscle fibers per nerve fiber • eye muscles • Strength control • gastrocnemius muscle has 1000 fibers per nerve fiber 11-37 Neuromuscular Junctions (Synapse) • Functional connection between nerve fiber and muscle cell • Neurotransmitter (acetylcholine/ACh) released from nerve fiber stimulates muscle cell • Components of synapse (NMJ) • synaptic knob is swollen end of nerve fiber (contains ACh) • junctional folds region of sarcolemma • increases surface area for ACh receptors • contains acetylcholinesterase that breaks down ACh and causes relaxation • synaptic cleft = tiny gap between nerve and muscle cells • Basal lamina = thin layer of collagen and glycoprotein over all of muscle fiber 11-38 The Neuromuscular Junction 11-39 Neuromuscular Toxins • Pesticides (cholinesterase inhibitors) • bind to acetylcholinesterase and prevent it from degrading ACh • spastic paralysis and possible suffocation • Tetanus or lockjaw is spastic paralysis caused by toxin of Clostridium bacteria • blocks glycine release in the spinal cord and causes overstimulation of the muscles • Flaccid paralysis (limp muscles) due to curare that competes with ACh • respiratory arrest 11-40 End of Lecture 11a • During lab • see slides of all three muscle tissues • look at models of same • review muscles (organs)