Muscles Ch.12 Our patient for the day... Name: Eddy Age: Newborn Whole-body muscle contractions No relaxation Severe difficulty breathing due to inadequate relaxation of breathing muscles Diagnosed with tetanus Stepping on a rusty nail with a certain type of bacteria can be baaaaaad Let’s talk about why. Our patient for the day... Name: Eddy Age: Newborn Whole-body muscle contractions No relaxation Severe difficulty breathing due to inadequate relaxation of breathing muscles Diagnosed with tetanus Signaling a muscle to start contraction ACh Nicotinic receptor Target: skeletal muscle CNS Figure 8.19a ESSENTIALS – Synaptic Communication Neurotransmitter Release An action potential depolarizes the axon terminal. Synaptic vesicle Action potential with neurotransmitter The depolarization opens arrives at molecules voltage- gated Ca2+ channels, axon terminal and Ca2+ enters the cell. Calcium entry triggers exocytosis of synaptic vesicle contents. Docking protein 2+ Ca Neurotransmitter diffuses Synaptic across synapse and binds to cleft post-synaptic receptors. Neurotransmitter binding initiates a response in the postsynaptic cell. Voltage-gated Receptor 2+ Postsynaptic cell Ca channel Cell response If this Somatic Motor Pathways Trigger Action Potentials Within Skeletal Muscle Synaptic vesicle (ACh) Ca2+ Ca2+ ACh Acetyl + choline Voltage-gated Ca2+ channels AChE Nicotinic receptors bind Skeletal muscle ACh, opening Na+ channels, fiber triggering action potentials and contraction in skeletal muscle. Why do APs in the muscle cause them to contract? To learn about something’s function, we can start by taking a look at its structure. Let’s take a look under the microscope Anatomy review Skeletal muscle composed of many of muscle fibers/cells Tendon Skeletal muscle (connects bone to muscle) Nerve and blood vessels Connective tissue Muscle fascicle: bundle of fibers Connective tissue Nucleus Muscle fiber Skeletal muscle composed of many of muscle fibers/cells Tendon Skeletal muscle (connects bone to Whole muscle muscle) Nerve and blood vessels Muscle fascicle Connective tissue Muscle fiber/cell Muscle fascicle: bundle of fibers Connective tissue Nucleus Muscle fiber Figure 12.1 THE THREE TYPES OF MUSCLES HAVE DIFFERING STRUCTURES/APPEARANCES Skeletal muscle fibers are large, multinucleate cells that appear striated (striped) under the microscope. Control the Nucleus movement of our skeleton Muscle fiber (cell) Striations *multinucleated=many nuclei in same cell Cardiac muscle fibers are also Nucleus striated but they are smaller, branched, and uninucleate. Cells are joined in series by junctions Muscle fiber called intercalated disks. Intercalated disk Striations Smooth muscle fibers are small, uninucleate, and lack striations. Nucleus Muscle fiber The basic functional unit of a myofibril is the sarcomere A band Sarcomere Z disk Z disk ANATOMY SUMMARY Myofibril M line I band H zone Titin Z disk Z disk M line Myosin crossbridges M line Thick filaments Thin filaments A band: overlap of thick and thin filaments I band: only thin filamentsTitin Troponin Nebulin Myosin heads Hinge Myosin tail region Tropomyosin G-actin molecule Myosin molecule Actin chain The basic functional unit of a myofibril is the sarcomere A band Sarcomere Z disk Z disk ANATOMY SUMMARY Myofibril M line I band H zone Titin Z disk Z disk M line Myosin crossbridges M line Thick filaments Thin filaments Titin Troponin Nebulin Myosin heads Hinge Myosin tail region Tropomyosin G-actin molecule Myosin molecule Actin chain Muscle cells and tissue use unique names for some common things End anatomy review Muscle fibers composed of subunits called myofibrils Mitochondria (energy source) Sarcoplasmic reticulum Nucleus Thick Thin filament filament T-tubules Now let’s look at one individual muscle fiber/cell and its part Myofibril Sarcolemma Sarcolemma=Cell membrane Sarcoplasmic Retic.=Modfied Endoplasmic Reticulum T-tubules=invaginations of sarcolemma Muscle fibers composed of subunits called myofibrils Mitochondria (energy source) Sarcoplasmic reticulum (Ca2+ storage) Nucleus T-tubules Sarcolemma (cell membrane) Sarcolemma=Cell membrane Sarcoplasmic Retic.=Modified Endoplasmic Reticulum T-tubules=invaginations of sarcolemma Figure 12.10a ESSENTIALS – Excitation-Contraction Coupling and Relaxation Slide 2 https://www.youtube.com/watch?v=8Hu5W_tFXLs Axon terminal of somatic motor neuron KEY DHP = dihydropyridine L-type calcium channel RyR = ryanodine receptor-channel Muscle fiber ACh nt ial Let’s look in a bit more detail about how e Somatic motor neuron releases calcium+ gets released from the sarcoplasmic Na ACh a neuromuscular junction. Action pot Action pot reticulum.... Motor end plate + RyR Net entry of Na through ACh receptor-channel initiates a T-tubule muscle action potential. Ca2+ Sarcoplasmic reticulum Z disk DHP Troponin Actin Tropomyosin M line Myosin head Myosin thick filament © 2013 Pearson Education, Inc. Figure 12.4 T-TUBULES HELP SPREAD ACTION POTENTIAL IN FIBER T-tubules are extensions of the cell membrane (sarcolemma) that associate with the ends (terminal cisternae) of the sarcoplasmic reticulum. T-tubule brings action potentials into interior Sarcoplasmic of muscle fiber. reticulum stores Ca2+. Sarcolemma AP in muscle fiber Triad Thick Thin Terminal filament filament cisterna Figure 12.10b ESSENTIALS – Excitation-Contraction Coupling and Relaxation Slide 5 https://www.youtube.com/watch?v=IOkn1ldFO60 DHP KEY DHP = dihydropyridine L-type calcium channel RyR = ryanodine receptor-channel RyR Action potential in t-tubule Let’s look in a bit more detailalters conformationabout ofhow DHP calcium gets released from thereceptor. sarcoplasmic DHP doesn’t open! DHP receptor opens RyR Ca2+ RyR reticulum.... release channels in sarco- DHP plasmic reticulum, and Ca2+ enters cytoplasm. Ca2+ released 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. © 2013 Pearson Education, Inc. Figure 12.8b (2 of 7) Slide 5 Figure 12.10b ESSENTIALS – Excitation-Contraction Coupling and Relaxation https://www.youtube.com/watch?v=sIH8uOg8ddw Slide 5 2+ Cytosolic Ca2+ Ca levels increase in cytosol. DHP Tropomyosin KEY shifts, exposing DHP = dihydropyridine L-type binding site on Ca 2+ binds calcium channelto actin. troponinRyR = ryanodine (TN). receptor-channel RyR Action potential in t-tubule Let’s look in a bit more detailTroponin-Caalters conformationabout2+ ofhow DHP TN complexreceptor. DHP pulls doesn’t open! calcium gets released from thetropomyosin sarcoplasmic Actin 2+ awayDHP receptor from opensactin RyR’s Ca RyR reticulum....moves release channels in sarco- myosin-binding site.2+ DHP ADP plasmic reticulum, and Ca enters cytoplasm. Power stroke Ca2+ released P Ca2+ binds to troponin, i Myosinallowing actin-myosin binds strongly binding. to actin and completes power stroke. Myosin thick filament Myosin heads execute power stroke. Distance actin moves ActinActin filament filament slides toward moves.center of sarcomere. See video for how myosin uses ATP to complete power stroke © 2013 Pearson Education, Inc. © 2013 Pearson Education, Inc. After death, an animal can experience rigor mortis, the state of rigidity due to sustained muscle contraction....even after death. Rigor mortis is due to lack of production of ATP. WTH?! NO ATP leads to sustained muscle contraction?!?! Let’s watch the video again... https://www.youtube.com/watch?v=sIH8uOg8ddw A normal muscle cell at rest (no sarcoplasmic Ca2+, ATP hydrolyzed into ADP + P by myosin) Ca2+ released Ca2+ not released A normal excited, muscle cell Binding sites for myosin unexposed, (sarcoplasmic retic. Ca2+ released) No contraction A normal excited, muscle cell (sarcoplasmic retic. Ca2+ released) Myosin binds to actin ATP present? Myosin detaches and hydrolyzes ATP. Myosin resets If Ca2+ still around too, generate another power stroke Myosin releases ADP and P, generates power stroke/force A normal excited, muscle cell (sarcoplasmic retic. Ca2+ released) Myosin binds to actin Rigor mortis: hours after death, SR membrane breaks down. Sarcoplasm Ca2+ Force generated Available ATP Myosin gets stuck in this Myosin releases ADP and P, generates conformation power stroke/force A normal excited, muscle cell (sarcoplasmic retic. Ca2+ released) Myosin binds to actin How do we get the muscle to relax normally? Myosin releases ADP and P, generates power stroke/force FigureFigure 12.10b12.10c ESSENTIALSESSENTIALS –– Excitation-ContractionExcitation-Contraction Coupling Coupling and and Relaxation Relaxation SlideSlide 5 3 https://www.youtube.com/watch?v=IOkn1ldFO60KEY DHP = dihydropyridine L-type calcium channel KEY RyR = ryanodine receptor-channel DHP = dihydropyridine L-type calcium channel Action potential in t-tubule Let’s look in a bit more detailaltersRyR conformation =about ryanodine receptor-channel ofhow DHP receptor. calcium gets released from theSarcoplasmic sarcoplasmic Ca2+-ATPase DHPpumps receptor Ca2+ backopens into RyR SR. Ca 2+ reticulum.... release channels in sarco- plasmic reticulum, and Ca2+ entersDecrease cytoplasm. in free cytosolic ATP [Ca2+] causes Ca2+ to unbind Ca2+ releasesCa2+ released Ca2+ from troponin. Ca2+ binds to troponin, allowing actin-myosin binding. Tropomyosin re-covers binding site. When myosin heads release, elastic elements pull MyosinMyosin thickthick filamentfilament Myosinfilaments heads back execute to their power relaxed stroke.position. Distance actinactin movesmoves Actin filament