Neuromuscular System II PDF

Neuromuscular System II P T 8 2 0 2 , A P P L I E D P H Y S I O LO GY Objectives Discuss the neuromuscular junction Describe excitation-contraction coupling Describe factors influencing force generation Describe how motor units function Identify characteristics of different muscle fiber types Th...

Neuromuscular System II P T 8 2 0 2 , A P P L I E D P H Y S I O LO GY Objectives Discuss the neuromuscular junction Describe excitation-contraction coupling Describe factors influencing force generation Describe how motor units function Identify characteristics of different muscle fiber types The Neuromuscular Junction Specialized synapse between a motoneuron and a muscle fiber Occurs at a structure on the muscle fiber called the motor end plate (usually only one per fiber)  Neuromuscular Junction (2 of 2) The Neuromuscular Junction Synaptic trough: invagination in the motor Synaptic cleft: end plate membrane − 20–30 nm wide − contains large quantities of acetylcholinesterase (AChE) Subneural clefts: − Increases surface area of postsynaptic membrane − ach-gated channels at tops − voltage-gated Na+ channel in bottom half xcitation of Skeletal Muscle: Neuromuscular Transmission mitochondria to address energy requirements for acetylcholine synthesis that is packaged into synaptic vesicles. (highly concentrated, ~10,000 Ach molecules per vesicle) Neuromuscular Junction ACh is stored in small synaptic vesicles ACh in turn excites the muscle fiber membrane The synaptic space has large quantities of acetylcholinesterase, which destroys acetylcholine a few milliseconds after it has been released  Excitation of Skeletal Muscle: Neuromuscular Transmission Nerve Impulses that reach the terminal result in the release of vesicles of acetylcholine (Ach) into the synaptic cleft/space. Nerve impulse reaches neuromuscular junctions Voltage-gated calcium channels in neuronal membrane open and allow Ca2+ to diffuse from synaptic space to the inside of the nerve Ca2+ activates Ca2+-Calmodulin dependent protein kinase Ca2+-calmodulin dependent protein kinase phosphorylates synapsin proteins which frees ACh vesicles that were anchored to the cytoskeleton ACh vesicles move to active zone of presynaptic neural membrane, docks at release sites, fuse with membrane and empty ACh into synaptic space (exocytosis) Excitation of Skeletal Muscle: Neuromuscular Transmission Nerve impulses that reach the terminal result in the release of vesicles of acetylcholine (Ach) into the synaptic cleft/space , and will: 1. Attach to the alpha subunits of the acetylcholine receptors 2. Be degraded by acetylcholinesterase into acetate and choline (actively reabsorbed into the terminal to be re-used for synthesis) Acetylcholinesterase mostly lines connective tissue in the synaptic space, though a small mount may be free [in the space].  Neuromuscular Transmission Acetylcholine receptors These acetylcholine-gated ion channels are near the openings of the subneural clefts and are comprised of five (5) transmembrane protein subunits: The channel undergoes conformational change when two (2) Ach molecules attach to the alpha subunits, opening the channel to allow Na+, K+, and Ca2+ ions (i.e., cations) to flow inward (especially Na+), while the highly negative charge of the channel at the opening repels anions. The resulting local, positive potential change (end plate potential) typically triggers adjacent voltage-gated sodium channels, which leads to greater Na+ influx…propagating an AP along the muscle membrane that leads to contraction. End Plate Potential to Muscle Fiber Excitation End plate potential Potential Na+ of local Voltage- Ach-gated channels pours area in gated Muscle Action in muscle into muscle Na+ contracti Potential membrane open muscle increase channels on fiber s by ~50 open mV Some end plate potentials are strong enough to cause enough sodium channels to open to start a positive feedback loop (sodium enters, more sodium channels open) and cause an AP Muscle Fiber Contraction: Excitation- Contraction Coupling 1. Action potential (AP) starts in brain 2. AP arrives at axon terminal, releases acetylcholine (ACh) 3. ACh crosses synapse, binds to ACh receptors on plasmalemma 4. Na+ pours into muscle fiber 5. Potential of local area in muscle increases & Voltage- gated Na+ channels open 6. AP travels down plasmalemma, T-tubules 7. Triggers Ca2+ release from sarcoplasmic reticulum (SR) 8. Ca2+ enables actin-myosin contraction Transverse Tubules and Excitation- Contraction Coupling Transverse Tubules (T tubules) transmit APs from the surface of muscle fibers deep to the level of the myofibrils They run transverse to the myofibrils They start at the cell membrane and penetrate all the way from one side of the muscle fiber to the other side Excitation-contraction coupling: AP travels along T tubules and near sarcoplasmic reticulum AP allows Ca2+ release from sarcoplasmic reticulum The influx of Ca2+ allows muscle contraction Role of Ca2+ in Muscle Contraction Sarcoplasmic Reticulum is composed of Terminal cisternae: Large chambers that abut the T tubules Long longitudinal tubules that surround all surfaces of the actual contracting myofibril Inside the sarcoplasmic reticulum is an excess of calcium ions in high concentration Role of Ca2+ in Muscle Contraction AP arrives at SR from T-tubule SR sensitive to electrical charge Causes mass release of Ca2+ into sarcoplasm Ca2+ binds to troponin on thin filament At rest, tropomyosin covers myosin-binding site, blocking actin- myosin attraction Troponin-Ca2+ complex moves Myosin binds to actin, contraction can occur Excitation-contraction Coupling https://www.youtube.com/watch?v=eRU4WVyVCYk  Excitation-Contraction Coupling Excitation - Depolarization of motor end plate Nerve impulse travels down T-tubules and causes release of Ca++ from SR Ca++ binds to troponin and causes position change in tropomyosin, exposing active sites on actin Permits strong binding state between actin and myosin and contraction occurs Excitation-Contraction Coupling Contraction 1.At rest, myosin cross-bridges in weak binding state. 2.Ca+2 binds to troponin, causes shift in tropomyosin to uncover active sites, and cross-bridge forms strong binding state. 3.Pi released from myosin, cross-bridge movement occurs. 4. ADP released from myosin. 5.ATP attaches to myosin, breaking the cross-bridge and forming weak binding state. Then ATP binds to myosin, broken down to ADP+Pi, which energizes myosin. Continues as long as Ca+2 and ATP are present. Muscle Relaxation AP ends, electrical stimulation of SR stops Ca2+ pumped back into SR Stored until next AP arrives Requires ATP Called the SR calcium ATPase pump Without Ca2+, troponin and tropomyosin return to resting conformation Covers myosin-binding site Prevents actin-myosin cross-bridging SR calcium ATPase pump Two isoforms found in adults SERCA1a found in Type II fibers SERCA2a found in Type I, cardiac and smooth muscle The ability to release and re-sequester Ca2+ may be one of the factors leading to fatigue with exercise Studies have shown that training programs involving all out sprint activity causes and increase in the amount of the two isoforms of SERCA Could be an adaption with exercise associated with greater recovery ability Ability to repeat intense activity associated with training Energy for Muscle Contraction ATP is required for muscle contraction Myosin ATPase breaks down ATP as fiber contracts ATP  ADP + Pi + energy Concentration of ATP in muscle fiber is sufficient to maintain full contraction for 1-2 seconds Ca2+ reuptake Actin/Myosin binding Sources of ATP Phosphocreatine (PC) Glycolysis Oxidative phosphorylation Factors influencing force generation Assessing Muscular Strength  Factors Influencing Force Generation NEURAL FACTORS CONTRACTILE FACTORS Orderly recruitment and the Skeletal muscle size principle Skeletal muscle architecture Rate coding Length-tension relationship Synchronization Contractile speed Contractile history Rate Coding Rates at which motor units discharge action potentials Length tension relationship Contraction Speed  Motor Units a-Motor neurons innervate muscle fibers Motor unit Single a-motor neuron + all fibers it innervates More operating motor units = more contractile force The finer the control required (e.g., rapid-moving small muscles) the fewer the # of fibers innervated by a motor unit. Integrated in the muscle to overlap other motor units Motor units Small motor units (e.g., larnyx, extraocular) − as few as 10 fibers/unit − precise control − rapid reacting Large Motor Units (e.g., quadriceps muscles) − as many as 1000 fibers/unit − coarse control − slower reacting Motor units overlap, which provides coordination Not a really good relation between fiber type and size of motor unit Motor Unit Properties Motor unit recruitment: process of adding motor units to increase force. Size principle: Motoneurons with progressively larger axons become recruited as muscle force increases. Selective recruitment and firing pattern of fast- twitch and slow-twitch motor units that control movement serve as the mechanism to produce the desired, coordinated response Muscle Fiber types Properties of Muscle Fiber Types Biochemical properties Oxidative capacity Type of ATPase Contractile properties Maximal force production Speed of contraction Muscle fiber efficiency Muscle Fiber Types Most muscles contain both types of fiber, but proportions differ All fibres in a particular motor unit will be of the same type, that is, fast or slow Fast and slow fibers show different resistance to fatigue Slow fibers (Type I) Fast fibers (Type II) – oxidative – glycolytic small diameter large diameter high myoglobin content low myoglobin content high capillary density low capillary density many mitochondria few mitochondria low glycolytic enzyme high glycolytic enzyme content content Type I Vs Type II Sarcoplasmic reticulum Type II fibers Faster Ca2+ release, 3 to 5 times faster speed of contraction More Ca2+, more binding sites Peak power: Effects of different SR, motor units, etc. Single muscle fiber recording Regardless of fiber type, all muscle fibers reach peak power at ~20% peak force Characteristics of Muscle Fiber Types Table 1.1 Characteristics of Muscle Fiber Types Fiber Type Determinants Fast, slow, and intermediate twitch type muscle can be identified by histochemistry. In any muscle there will be a mixture of slow and fast fibers. Motor units containing slow fibers will be recruited first to power normal contractions. Fast fibers help out when particularly forceful contraction is required. Different people have different proportions of these types. Genetic factors Determine which a-motor neurons innervate fibers Fibers differentiate based on a-motor neuron Training factors Endurance versus strength training, detraining Can induce small (10%) change in fiber type – important to remember the fiber does not change merely the characteristics of that muscle change Aging: muscles lose type II motor units – become offline or less efficient Thanks & have a great long weekend