Physiology: Chp 12 B PDF

Physiology: Chp 12 B Autonomic & Somatic Motor Control Juan J. Bustamante, Ph.D. Assistant Professor Pharmaceutical Science Phone (361) 221-0643 Email: [email protected] Office: Room 223 © 2016 Pearson Educ...

Physiology: Chp 12 B Autonomic & Somatic Motor Control Juan J. Bustamante, Ph.D. Assistant Professor Pharmaceutical Science Phone (361) 221-0643 Email: [email protected] Office: Room 223 © 2016 Pearson Education, Inc.  Which of the following pairings between ligand and receptor is NOT correct? a. norepinephrine: beta adrenergic b. norepinephrine: muscarinic cholinergic c. epinephrine: alpha adrenergic d. ACh: nicotinic cholinergic © 2016 Pearson Education, Inc.  Which of the following pairings between ligand and receptor is NOT correct? a. norepinephrine: beta adrenergic b. norepinephrine: muscarinic cholinergic c. epinephrine: alpha adrenergic d. ACh: nicotinic cholinergic © 2016 Pearson Education, Inc.  Which phrase best explains the binding affinity of adrenergic alpha receptors for epinephrine (E) and norepinephrine (NE)? a. NE > E b. E > NE c. E = NE © 2016 Pearson Education, Inc.  Which phrase best explains the binding affinity of adrenergic alpha receptors for epinephrine (E) and norepinephrine (NE)? a. NE > E b. E > NE c. E = NE © 2016 Pearson Education, Inc.  The enzyme acetylcholinesterase (AChE) breaks down a. GABA. b. carbachol. c. catecholamines. d. acetylcholine. e. glutamate. © 2016 Pearson Education, Inc.  The enzyme acetylcholinesterase (AChE) breaks down a. GABA. b. carbachol. c. catecholamines. d. acetylcholine. e. glutamate. © 2016 Pearson Education, Inc.  Organophosphate insecticides inhibit cholinesterase so symptoms of poisoning by these compounds include which of the following? a. muscle cramps and paralysis b. hypotension c. pupil constriction d. increased salivation e. All of the above © 2016 Pearson Education, Inc.  Organophosphate insecticides inhibit cholinesterase so symptoms of poisoning by these compounds include which of the following? a. muscle cramps and paralysis b. hypotension c. pupil constriction d. increased salivation e. All of the above © 2016 Pearson Education, Inc. Figure 11.10d Somatic Motor Neurons and the Neuromuscular Junction An action potential arrives at the axon terminal, causing voltage-gated Ca2+ channels to open. Calcium entry causes synaptic vesicles to fuse with the presynaptic membrane and release ACh into the synaptic cleft. Presynaptic membrane Synaptic vesicle (ACh) Synaptic cleft Ca2+ Ca2+ ACh Acetyl + choline Postsynaptic Voltage-gated membrane is Ca2+ channel modified into a motor end plate. AChE Nicotinic Skeletal muscle receptor fiber Acetylcholine (ACh) is metabolized by acetylcholinesterase (AChE). © 2016 Pearson Education, Inc. Figure 11.6 Sympathetic and parasympathetic neurotransmitters and receptors Sympathetic pathways Parasympathetic pathways use acetylcholine and use acetylcholine. norepinephrine. CNS CNS preganglionic neurons release acetylcholine ACh postganglionic cell Nicotinic receptor (nAChR) Autonomic ganglion Postganglionic Postganglionic sympathetic neurons parasympathetic secrete neurons secrete Norepinephrine ACh Adrenergic (NE) Muscarinic receptor receptor (mAChR) T Target tissue T © 2016 Pearson Education, Inc.  Autonomic Pathways Control Smooth and Cardiac Muscle and Glands The neuroeffector junction is the synapse between a postganglionic autonomic neuron and its target cells (effector). Note: The structure of an autonomic synapse differs from the model synapses © 2016 Pearson Education, Inc. Figure 11.7b Autonomic synapses Slide 9 Sympathetic neuroeffector Junction Norepinephrine (NE) release and removal at a sympathetic neuroeffector junction Action potential arrives at the varicosity. Depolarization opens voltage-gated Ca2+ channels. Axon varicosity Ca2+ entry triggers MAO exocytosis of synaptic vesicles. Tyrosine Axon NE binds to adrenergic receptor on target. NE Action potential Receptor activation ceases when Exocytosis NE diffuses away from the synapse. Voltage-gated Ca2+ channel Active transport Ca2+ NT removal NE is removed from the synapse. NE Diffuses away Blood G NE can be taken back into vessel synaptic vesicles for re-release. Response Adrenergic Target cell NE is metabolized by receptor monoamine oxidase (MAO). © 2016 Pearson Education, Inc. Figure 8.20 Synthesis and recycling of acetylcholine Slide 1 Parasympathetic neuroeffector Junction Ach is synthesized from choline and acetyl CoA in the varicosities Note: There are 2 types of cholinergic receptors Mitochondrion 1. Muscarinic Acetyl CoA CoA 2. Nicotinic Axon Acetylcholine (ACh) is made terminal Enzyme from choline and acetyl CoA. A Acetylcholine Ch A Synaptic Ch vesicle In the synaptic cleft, ACh is rapidly Ch broken down by the enzyme acetylcholinesterase. A Ch Choline is transported back into the axon terminal by cotransport Na+ Ch Choline Cholinergic with Na+. A receptor A Ch Recycled choline is used to make Acetate Acetylcholinesterase (AChE) Postsynaptic more ACh. cell © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc.  Organophosphate insecticides inhibit cholinesterase so symptoms of poisoning by these compounds include which of the following? a. muscle cramps and paralysis b. hypotension c. pupil constriction d. increased salivation e. All of the above © 2016 Pearson Education, Inc.  Slide 3 Calcium release from the sarcoplasmic reticulum is mediated by two membrane proteins. L-type calcium channel dihydropyridine (DHP) receptor and ryanodine receptors (RyR) © 2016 Pearson Education, Inc.  Slide 6 KEY DHP = dihydropyridine L-type calcium channel RyR = ryanodine receptor-channel Action potential in t-tubule Excitation-Contraction Coupling alters conformation of DHP receptor. - + - + - + DHP receptor opens RyR Ca2+ - + T-tubule release channels in sarco- Sarcoplasmic × plasmic reticulum, and Ca2+ reticulum enters cytoplasm. - + + - + + - - - Ca2+ released. Actin Ca2+ binds to troponin, allowing actin-myosin binding. Myosin thick filament Myosin heads execute power stroke. Distance actin moves Actin filament slides toward center of sarcomere. © 2016 Pearson Education, Inc. Figure 12.10c Excitation-Contraction Coupling and Relaxation Slide 4 Relaxation Phase KEY DHP = dihydropyridine L-type calcium channel RyR = ryanodine receptor-channel Relaxation Phase + - + - Sarcoplasmic Ca2+-ATPase + - pumps Ca2+ back into SR. T-tubule + - Sarcoplasmic × reticulum + - ATP Decrease in free cytosolic + ++ - [Ca2+] causes Ca2+ to unbind - - - Ca2+ releases. Ca2+ from troponin. Actin Tropomyosin re-covers binding site. When myosin heads release, Myosin thick filament elastic elements pull filaments back to their relaxed position. Distance actin moves A muscle twitch is a single contraction-relaxation cycle © 2016 Pearson Education, Inc. Figure 12.8 Troponin and tropomyosin Relaxed state. Myosin head cocked. Tropomyosin Initation of contraction. A calcium signal partially blocks binding site on actin. Myosin is initiates contraction. weakly bound to actin. Cytosolic Ca2+ Ca2+ levels increase in cytosol. Troponin G-actin Tropomyosin shifts, exposing binding site on actin. Ca2+ binds to troponin (TN). Troponin-Ca2+ TN TN complex pulls Myosin head tropomyosin Actin Tropomyosin moves away from actin’s ADP myosin-binding site. ADP Pi Power stroke Pi Myosin binds strongly to actin and completes power stroke. Actin filament moves. © 2016 Pearson Education, Inc. Figure 12.8b Troponin and tropomyosin Slide 1 Initation of contraction. A calcium signal initiates contraction. Cytosolic Ca2+ Ca2+ levels increase in cytosol. Tropomyosin shifts, exposing binding site on actin. Ca2+ binds to troponin (TN). Troponin-Ca2+ TN complex pulls Actin tropomyosin moves away from actin’s ADP myosin-binding site. Power stroke Pi Myosin binds strongly to actin and completes power stroke. Actin filament moves. © 2016 Pearson Education, Inc. Figure 12.8b Troponin and tropomyosin Slide 2 Initation of contraction. A calcium signal initiates contraction. Cytosolic Ca2+ Ca2+ levels increase in cytosol. TN ADP Pi © 2016 Pearson Education, Inc. Figure 12.8b Troponin and tropomyosin Slide 3 Initation of contraction. A calcium signal initiates contraction. Cytosolic Ca2+ Ca2+ levels increase in cytosol. Ca2+ binds to troponin (TN). TN ADP Pi © 2016 Pearson Education, Inc. Figure 12.8b Troponin and tropomyosin Slide 4 Initation of contraction. A calcium signal initiates contraction. Cytosolic Ca2+ Ca2+ levels increase in cytosol. Tropomyosin shifts, exposing binding site on actin. Ca2+ binds to troponin (TN). Troponin-Ca2+ TN complex pulls tropomyosin away from actin’s ADP myosin-binding site. Pi © 2016 Pearson Education, Inc. Figure 12.8b Troponin and tropomyosin Slide 5 Initation of contraction. A calcium signal initiates contraction. Cytosolic Ca2+ Ca2+ levels increase in cytosol. Tropomyosin shifts, exposing binding site on actin. Ca2+ binds to troponin (TN). Troponin-Ca2+ TN complex pulls tropomyosin away from actin’s ADP myosin-binding site. Power stroke Pi Myosin binds strongly to actin and completes power stroke. © 2016 Pearson Education, Inc. Figure 12.8b Troponin and tropomyosin Slide 6 Initation of contraction. A calcium signal initiates contraction. Cytosolic Ca2+ Ca2+ levels increase in cytosol. Tropomyosin shifts, exposing binding site on actin. Ca2+ binds to troponin (TN). Troponin-Ca2+ TN complex pulls Actin tropomyosin moves away from actin’s ADP myosin-binding site. Power stroke Pi Myosin binds strongly to actin and completes power stroke. Actin filament moves. © 2016 Pearson Education, Inc. Figure 12.9 The contraction cycle Slide 1 Tight Binding in the Rigor State G-actin molecule Myosin binding sites ATP binds to myosin. Myosin filament Myosin releases actin. NAVIGATOR ATP binds. ADP releases. Myosin hydrolyzes ATP. Energy Myosin releases ADP at the from ATP rotates the myosin head end of the power stroke. Contraction- relaxation to the cocked position. Myosin binds weakly to actin. The Power Stroke Sliding filament Actin filament moves toward M line. Relaxed state. Head ADP Ca2+ swivels. Pi signal ADP and Pi Myosin Power stroke begins remain bound. releases Pi. when tropomyosin (not shown) moves off the binding site. © 2016 Pearson Education, Inc.  Sliding Filament Theory Actin and myosin slide past each other during contraction Power stroke cycle: myosin crossbridges move actin filament – Calcium release from T-tubules – Calcium binds troponin – Troponin pulls tropomyosin from myosin-binding sites on actin – Myosin binds tightly to and moves actin – Rigor: myosin stays tightly bound to actin until ATP binds to myosin which is released from actin © 2016 Pearson Education, Inc.  Sliding Filament Theory – Myosin breaks down ATP – The energy rotates the myosin head that binds weakly to actin down the molecule – Head of myosin is cocked ready for the next power stroke ATP must bind to myosin to release myosin from actin Rigor mortis: muscles “freeze” if no ATP is available to release myosin Relaxation: Calcium ions pumped back to sarcoplasmic reticulum © 2016 Pearson Education, Inc. Figure 12.7 Summary map of muscle contraction © 2016 Pearson Education, Inc.  Skeletal Muscle Usually attached to bones by tendons Origin: closest to the trunk or to more stationary bone Insertion: more distal or more mobile attachment Flexor: brings bones together Extensor: moves bones away Antagonistic muscle groups: flexor-extensor pairs © 2016 Pearson Education, Inc. Figure 12.3a Skeletal Muscles Muscle cells are called muscle fibers Fused cells with many nuclei Satellite cells differentiate into muscle Cells bundled into fascicles surrounded by connective tissue © 2016 Pearson Education, Inc. Figure 12.3b Skeletal Muscles Structure of a Skeletal Muscle Fiber Mitochondria Sarcoplasmic reticulum Nucleus Thick Thin filament filament T-tubules Myofibril Sarcolemma Myofibrils are the contractile structures Actin: thin filament Myosin: thick filament Fiber internal structures Accessory proteins: troponin and Sarcolemma: cell membrane tropomyosin Sarcoplasm: cytoplasm Sarcoplasmic reticulum: endoplasmic reticulum Network of transverse tubules: T-tubules connected with the sarcolemma © 2016 Pearson Education, Inc. Figure 12.5de The Sarcomere The sarcomere shortens during contraction. As contraction takes place, actin and myosin do not change length but instead slide past one another. I band A band Z Muscle Relaxed Myosin Actin Half of Z line Sarcomere I band H zone Half of shortens with I band contraction. Muscle Contracted H zone and I band both shorten, while A band remains constant. I H I © 2016 Pearson Education, Inc. Figure 12.15 Length-tension relationships Contraction Force Sarcomeres contract with optimum force if it at optimum length (neither too long nor too short) before the contraction begins. The tension generated by a muscle fiber is directly proportional to the number of crossbridges formed between the thick and thin filaments. 100 Tension (percent of maximum) 80 60 40 20 0 Adapted from A.M. Gordon et al., J Physiol 184: 1.3µ m 2.0µ m 2.3µ m 3.7µ m 170–192, 1966. Decreased Increased length Optimal length resting length © 2016 Pearson Education, Inc.  Muscle Contraction Muscle tension: force created by muscle Load: weight or force opposing contraction Contraction: creation of tension in muscle – Events at the neuromuscular junction – Excitation-contraction coupling – Sliding filaments Relaxation: release of tension © 2016 Pearson Education, Inc. Figure 12.16a Summation of contractions Single Twitches: Muscle relaxes completely between stimuli ( ). One twitch Tension 0 100 200 300 400 500 Time (msec) © 2016 Pearson Education, Inc. Figure 12.16b Summation of contractions Summation: stronger contraction when the muscle does not relax completely between action potentials. Summation: Stimuli closer together do not allow muscle to relax fully. Summed twitches Tension 0 100 200 300 400 500 Time (msec) © 2016 Pearson Education, Inc. Figure 12.16c Summation of contractions Summation Leading to Unfused Tetanus: Stimuli are far enough apart to allow muscle to relax slightly between stimuli. Unfused tetanus Maximum tension Tension Time (msec) © 2016 Pearson Education, Inc. Figure 12.16d Summation of contractions Summation Leading to Complete Tetanus: Muscle reaches steady tension. If muscle fatigues, tension decreases rapidly. Tetanus: maximal contraction Complete tetanus Maximum tension Tension Fatigue causes muscle to lose tension despite continuing stimuli. Single-twitch tension 0 Time (msec) © 2016 Pearson Education, Inc. Figure 12.13 Muscle fatigue Why do we eat bananas for muscle cramps?” Decrease calcium release due to neuron Maximal exercise or muscle K+ leaves muscle fiber, leading to increased extracellular concentration, altering the membrane potential Changes Na+_K+_ATPase activity © 2016 Pearson Education, Inc.  Contraction Force Motor unit: group of muscle fibers that function together and the somatic motor neuron that controls them Recruitment of additional motor units by the nervous system increases contraction force Asynchronous recruitment of motor units helps avoid fatigue – Different motor units take turns maintaining tension © 2016 Pearson Education, Inc. Figure 12.17 Motor units One muscle may have many motor units of SPINAL CORD different fiber types. Neuron 1 Neuron 2 Neuron 3 Motor nerve KEY Motor unit 1 Muscle Motor unit 2 fibers Motor unit 3 © 2016 Pearson Education, Inc.