BIOM 121 1nd Edition Lecture 16 Outline of Last Lecture I. Structure of a Muscle Fiber (Cell)II. The Skeletal Muscle FiberIII. The MyofibrilIV. SarcomereV. The Nerve-Muscle RelationshipOutline of Current Lecture I. The Neuromuscular JunctionII. Myasthenia GravisIII. Electrically Excitable CellsIV. Skeletal Muscle Fiber StimulationV. Rigor MortisCurrent LectureI. The Neuromuscular Junction (Continued)a. Junctional foldsi. Acetylcholine receptors; ~50 millionii. Folds increase surface areaII. Myasthenia Gravisa. Autoimmune diseaseb. Found in women of ages 20 – 40c. Body produces antibodies and they bind to acetylcholine receptors and blocks acetylcholine from binding to receptorsd. Can’t get efficient muscle contractione. Large portion of receptors are blocked by antibodiesf. DiagnosisThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.i. Have them look up: after 60 seconds, one eyelid will start to droop and then eyelid will completely close ii. Problems with all types of skeletal movementg. Treatments:i. Cholinesterase inhibitors – allows acetylcholine to not be broken down; acetylcholine may eventually be able to beat of antibodiesii. Immunosuppressive agents – suppresses production of antibodiesiii. Thymus removal (thymectomy) – removes ability to make T cellsiv. Plasmapheresis – remove blood, take out plasma (where antibodies are), and put it back; tube used often causes infectionIII. Electrically Excitable Cellsa. Muscle fibers and neuronsb. Electrophysiology: study of the electrical activity of cellsc. Voltage (electrical potential)d. Resting membrane potential (RMP): electrical difference for un-stimulated cell = -90 mVi. Chloride and sodium concentrations are high outside the cellii. Potassium and other anions are high in concentration inside the celliii. Anion charges are large and cannot move across cell membranee. Stimulation of cell causes channels to open up, potassium goes out, sodium comes in and membrane potential becomes very positive (this process creates action potential)f. Graphical representation of action potentiali. Un-stimulated cell = -90mVii. Depolarization: stimulated cell (sodium channels open) = + membrane potential 1. Bigger opening in sodium channels causes steeper slopeiii. Repolarization: sodium channels close and potassium channels open; removes a lot of positive charge and membrane potential again becomes negative; could also be caused by adding negative charge into celliv. Hyperpolarization: potassium channels remain open after the potential reaches resting/un-stimulated level; charge temporarily goes below -90mVv. Potassium channels are slow to open and slow to close; sodium channels open and close very quicklyIV. Skeletal Muscle Fiber Stimulationa. Four major phases of contraction and relaxation:i. Excitation1. Arrival of a nerve signal/action potentiala. Opens voltage gated calcium channels on synaptic knob b. Calcium enters synaptic knobc. Binds to synaptic vesicles that contain acetylcholined. Vesicles undergo exocytosis into synaptic clefte. Acetylcholine then binds to receptors2. Acetylcholine (Ach) releasea. Receptor binds to acetylcholine (2 molecules to each receptor)b. Activates receptor meaning it opens upi. Ligand-regulated ion gate (channel)ii. End-plate potential (EPP) generated: local change inmembrane potentialc. Acetylcholine receptors allow sodium in and potassium outwhich changes membrane potentials3. End plate potential  action potential – enough end plate potentials must add up to get an action potential to fire4. In action potential, open sodium and potassium gatesii. Excitation-contraction coupling1. Release of calcium from sarcoplasmic reticulum links excitation to contraction2. Voltage travels down T tubule and calcium released into sarcoplasm and links with troponin3. Calcium binding to troponin cause tropomyosin to roll away making actin available to bind to myosiniii. Contraction1. Myosin ATPase enzyme in myosin head hydrolyzes an ATP molecule (ATPADP + inorganic phosphate) can now use this as energy2. The head is in a “cocked” position and is activated 3. In order for myosin to bind to actin, it must release the ADP and inorganic phosphate4. Power stroke – pulling of the myosin head, requires one molecule of ATP5. As soon as it release actin, ATP binds to myosin6. If no hydrolysis of ATP occurs, then there’s no contractioniv. Relaxation1. Occurs when ATP binds back to myosin causing myosin to release actin2. Nerve stimulation stops3. ACh release stops4. Acetyl-cholinesterase (AChE) breaks down Ach5. Need to get rid of calcium; calcium is reabsorbed into sarcoplasmic reticulum and rebinds to protein called calsequestrin6. Tropomyosin re-blocks the active site7. Muscle fiber returns to its resting lengthV. Rigor Mortis – hardening of muscles and stiffening of bodya. Muscle relaxation requires ATPb. In rigor mortis, when someone dies, there is still some ATP activity going on but cells begin to die and deteriorate, releasing all cellular content including calciumc. ATP hydrolysis and calcium release causes muscles to contract, but with no addition of ATP after that, there is no relaxation that follows contractiond. Rigor mortis last about 48 hours and then the body begins to relax due to deterioration of all