Neuromuscular A&P

1. 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

2. 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?

3. 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)

4. Types of Muscle Tissue Skeletal* muscle tissue striated & voluntary studied as the muscular system Cardiac muscle tissue striated & autorhythmic Smooth muscle tissue nonstriated & involuntary

5. Skeletal Muscle • Long, cylindrical, unbranched cells with striations and multiple peripheral nuclei • movement, facial expression, posture, breathing, speech, swallowing and excretion

6. 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

7. 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

8. Myasthenia Gravis Drooping eyelids and weakness of muscles of eye movement

9. Cardiac Muscle • Short branched cells with striations and intercalated discs • one central nuclei per cell • Pumping of blood by cardiac (heart) muscle

10. 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. 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

12. 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

13. 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

14. Types of Smooth Muscle • Multiunit smooth muscle • largest arteries, iris, pulmonary air passages, arrector pili muscles • terminal nerve branches synapse on myocytes • independent contraction

15. 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

16. Stimulation of Smooth Muscle

17. 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

18. 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

19. 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)

20. Contraction of Smooth Muscle

21. 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

22. “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*

26. A Myofiber

27. 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

28. 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

29. 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

30. Elastic Filaments • Springy proteins called titin • Anchor each thick filament to Z disc • Prevents overstretching of sarcomere

31. 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, • troponin moves tropomyosin off the actin active sites

32. Overlap of Thick and Thin Filaments

33. 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

34. Striations and Sarcomeres

35. 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

36. 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

37. 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

38. 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

39. The Neuromuscular Junction

40. 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

41. End of Lecture 11a • During lab • see slides of all three muscle tissues • look at models of same • review muscles (organs)