Human Physiology Muscle System - BIOL3205 PDF

Human Physiology BIOL3205 Muscle system Prof. Chi Bun Chan School of Biological Sciences 5N10 Kadoorie Biological Sciences Building [email protected] 39173823  Lecture outline Muscle types and their structural...

Human Physiology BIOL3205 Muscle system Prof. Chi Bun Chan School of Biological Sciences 5N10 Kadoorie Biological Sciences Building [email protected] 39173823  Lecture outline Muscle types and their structural characteristics Mechanism of muscle contraction Muscle contraction mechanics Control of muscle contractions Muscle metabolism and fatigue Muscle diseases  Classification of muscles unstriated Structural Skeletal Cardiac Smooth classification – ↓Y striated vs smooth unstriated striated ↳ Control methods can only be controlled by autonomous system Voluntary or IIII) involuntary Locations – Skeletal muscle, heart (Cardiac), hollow organs (e.g. intestinal smooth) by metabolic Metabolic fast twitch —> glucose slow twitch —> lipid classification – fast- fast —> contraction quickly twitch and slow- slow —> contraction and relax slowly twitch muscle twitch = contraction  Characteristics of muscle types branded (only in cariliad one nucleus only ⑳ b multiple nucleus & in one single cell O O G different mechanism to develop each muscle —> different single piece structure  skektal I Muscular system ~ 50% of total body weight (~ stem cell —> proripotent —> generate all cel satellite cell —> generate only muscle cell differentiate to mature muscle fiber 600 pieces) nutrients Satellite cell —> fuse multiple cell —> long bundle ~ Composes connective tissues, blood vessels, satellite cells, Myofiber and muscle fiber/ myofiber/myocytes Functions Gesture maintenance Locomotion move from one place to another —> thru coordinated actions of muscle and skeletal structures Organ movement – e.g. eye —> voluntary muscle eye Propulsion of contents through hollow internal organs involve smooth muscle involuntary Breathing around lung —> breathing Accomplishes work pushing/pulling —> work (https://www.healthline.com/health/how-many-muscles-are-in-the-human-body#muscle-facts)  Shapes of muscle largest organ —> 50% BW DONT RMB name multiple tendon here for abdomen linked by tendon (white) main idea: have multiple types and shapes of skeletal muscle muscle in eye —> contract —> reduce side in central opening Similarcontract Inher ↓ size reduce of centre (https://doctorlib.info/anatomy/classic-human-anatomy-motion/7.html)  Properties of muscle https://en.wikipedia.org/wiki/Muscle_contraction Excitability – able to an action potential in response to a neuronal stimulus can generate AP by its own - Contractility - able to shorten the tissue length (i.e. contraction) to a stimulus contract —> shortened Extensibility – able to extend when is stretched without being damaged put down DB —> stretched/lengthen Elasticity – able to return to its original structure when released special protein called titin —> basic unit of skeletal muscle to generate force —> elastic material —> stretch —> force —> relax —> pull muscle back to original structure similar pattern —> generate own AP heart (https://encyclopedia.pub/entry/8786) can also G AP but pattern different (https://doctorlib.info/physiology/medical-physiology-molecular/8.html)  Skeletal muscles are working in pairs Flexor contract gastrocnemius —> lifting foot up contract quad —> extend food ==> coordination to lift body up ext Extensor bicep contract —> shorten length ==> pull arm upward (reduce elbow angle (flexion by flexor) tricep contract —> shorten length ==> pull forearm down (increase elbow angle) (extension by extensor) A single muscle is attached to two bones across a joint – lever system Cannot actively push (lengthen) but pull (shorten) Antagonistic muscle group works together for flexion or extension to get job done —> one contract one relax Works in synergy coordinated —> cannot contract both  Skeletal muscle structure Connective tissues (better strength) Epimysium – wrapping a piece of muscle tissue Perimysium – wrapping a fascicle Endomysium – wrapping a muscle fiber single muscle cell - - Blood vessels there are other cells within fascicle bundle of myofiber Nerves – motor neurons, stripe —> myofibril sensory neurons determine contraction status multiple fascicle —> muscle Fasciclesfibre bundle of myofiber (muscle Myofiber one single muscle cell long fiber 6 (Gotti et al App Materials Today 2020 20: 100772) Myofibril polymer of structure 80% of cell volume occupied by myofibril epimysium perimysium ·mus) each of this —> sarcomere a protein structure cylindrical intracellular structure Contractile elements (80% vol of a myofiber) cause contraction of skeletal muscle Muscle anatomy and structure 80% of cell volume occupied by myofibril contraction of muscle O F protein structure masche fibler all) Muscle fiber (myofiber)  Fascicle  Whole muscle (e.g. Gastrocnemius) Size  Size myofibril dark and light structure —> stripe (phtection)  Myofibril structure actual I band Myofibril Contractile elements of the myofiber blue: thin 80% vol of the myofiber red: thick Sacromere one red surrounded by six thin Precise hexagonal geometry of microfilaments —> hexagonal Sarcomere the area between two dark line (Z line) I-band women H-zone I-band H zone lighter bc actin not touching all the way to M plate functional unit to generate force regular arrangement of highly organized cytoskeletal microfilaments (thick & thin) Variable length but constant size M (middle) line protrusion —> myosin filament (thick) A-band holds the thick filament together Electron microscope A (anisotropic) band (dark) We z Z-line M-line Z-line Stacked of thick and portions of thin filaments M-line H (Helles) zone (free of thin filament) Z-line darker bc denser filament (actin + myosin) I (isotropic) band (light) Thin filament only Z (zwischen)-line anchor thin line protrusion —> actin filament (thin) - (Crocini & Gotthardt Biophys Rev 2021 12: 637)  Hexagonal arrangement Microfilaments organization of filaments contract muscle —> head bend towards the tail during relaxed all binding site blocked by tropomyosin tropomyosin: prevent interaction between myosin and actin Thick filament enzyme —> can bind ATP —> useful for muscle contraction Myosin molecules (two identical subunits) twisted in a “golf club” shape dimmer of myosin Bend at hinge points 2 actin chains twist with each other —> thin filament Cross bridges Projections toward the thin enzyne protein: sense signal and ask tropomyosin to remove from & blotr binding site filament & protein polymer twist active sites Actin-binding site ATPase tail to tail connection OOg Thin filament g prevent interaction between thin and thick filement Actin – the backbone of thin - A band filament Tropomyosin – prevents the binding of cross bridges Troponin – Stabilizing the tropomyosin and actin * interaction, Ca2+ sensing Z-line titin linking Z line to myosin used to return to original structure - Z-line I band Z-line  Sliding filament mechanism Muscle contraction is a result of sarcomere shortening (i.e. the length between z lines) thick and thin interact with each other contract —> squeeze the structure —> shorten Sliding filament mechanism - thin filaments slid inward over the stationary thick filament move all sarcomere in myofibril to contract Constant length of filament but a change of I band and H zone width push actin toward center of H zone (M line) I band become shorter (I band = actin only region) H zone become shorter (myosin only region) titin linking Z line to myosin used to return to original structure length of thick and thin filament fixed maintain same width —> A band size not changed A band = thick filament size  Mechanism of skeletal muscle contraction voluntary muscle —> need input from brain Alpha motor neurons – neurons whose motor area activated —> motor neuron —> connected to a piece of muscle axons innervate skeletal muscle fibers 6 apply with neres Motor unit – motor neuron + all muscle fibers i I signal control multiple myofiber/cells can -. one motor neuron Muscle fibers of the same motor unit are not necessarily adjacent to each other multiple connection point one signal control multiple - Simultaneously activation of all muscle fibers in the same motor unit one single neuron can connect to multiple muscle cell but each single myofiber has one neuronal connection one contacting point —> neuromuscular junction (https://www.simplypsychology.org/motor-neuron.html)  Mechanism of skeletal muscle contraction AP coming —> trigger CA uptake —> exocytosis —> to cleft terminal button connecting point neurotransmitter motor end plate Na channel —> influx of sodium (synapse one neuron output —> generated local GP —> End-plate potential Neuromuscular junction (NMJ) -encotransmitter one GP form always trigger AP Terminal button and motor end plate (easy to reach threshold) AP different from neuron (neuron —> one direction to end) in skeletal muscle —> go both direction (NMJ usually in middle of muscle —> spread —> contract) Acetylcholine (Ach) receptor generates the end-plate no ISPS in skeletal muscle potential (EPP) similar to EPSP signal always ask muscle to control to relax —> simply stop condicurus(?) conduction Depolarization of the muscle plasma membrane Excitation-contraction coupling – sequence of events by which an AP activates the force-generation mechanism (https://youtu.be/pBOXHJQt-LI?si=s3q4JwdKEbCpUcuf)  Mechanism of skeletal muscle how to stop ?????? contraction Ca2+-dependent process Dihydropyridine Release from the sarcoplasmic reticulum Ryanodine receptor receptor Changes the shape of troponin, allowing tropomyosin to move away from the myosin- binding site Terminated when the cytosolic Ca2+ returns to basal level by the action of Ca2+-ATPase (ATP consuming) surface of skeletal muscle not smooth T-tubule —> well like —> cause sliding model linked to intracellular structure (sacroplasmic reticulum) —> has lot of calcium inside when current AP reach t tubule change structure of DHP receptor (linked to ryanodine receptor (channel)) receptor open —> change R receptor — >release of Ca from reticulum —> major causing factor of sliding model C troponin —> calcium sensor calcium bind —> change structure —> shift location of tropomyosin away from the binding site of actin myosin as long as there is Ca —> thick and thin filament interact with each other keep sliding (contracting) get rid of Ca to stop & & Ca pump (Ca ATPase) actively absorb Ca back to organelle with expense of ATP —> stop muscle contraction need ATP & Mechanism of skeletal & & Tropomyosin muscle contraction ATP charge myosin head —> make it ready to get stroke power thin filament blocked by tropomyosin Ca+ —> shift tropomyosin location actin myosin can bind once bind to myosin —> immediately perform enzymatic reaction Cross-bridge cycle – ATP —> ADP + Pi once Ca present —> bind sequence of repeated events & that a cross-bridge binds to a thin filament ATP can bind again actin and myosin detach each other myosin head bend detachment of cross bridge Consists of (1) attachment of the bridge to a thin filament; still interacting with each other release ADP & Pi out (2) movement/bending of - head of myosin bend toward M line the cross-bridge (Power - dragging actin - stroke); (3) detachment of - - the cross-bridge; (4) to make muscle relax —> detachment energizing the cross-bridge —> need ATP without ATP —> actin myosin keep contacting —> cannot relax will feel fatigue when ATP not enough ATP-dependent titin link myosin to Z line —> not returning to original structure  Rigor mortis Rigor mortis – postmortem stiffening of the body Smaller muscles over the face are the muscles where rigor mortis first appears, followed by rigor mortis of the muscles in the hands and upper limbs, and finally appears in the large muscles of the lower limbs. takes time to deplete all ATP Appears approximately 2 hours after death in the muscles of the face, progresses to the limbs over the next few hours, completing between 6 to 8 hours after death. Caused by depletion of ATP  Muscle Contraction - Cross Bridge Cycle Isotonic, Isometric, Eccentric and Concentric Muscle Contractions https://www.youtube.com/watch?v=BVcgO4p88AA https://www.youtube.com/watch?v=DkCcn9iBczw  Type of skeletal muscle contraction (Fores Contraction – activation of the force-generating Tension site contraction in physiological POV —> not shortening muscle Isotonic contraction tension = force Tension – force exerted on an object by a Load contracting muscle Load – force exerted on the muscle by an object Isometric concentration – muscle develops 2 hold the load # tension but - does not shorten or length muscle contraction involved myosin keeps bending bending force = load Isotonic contraction – muscle length changes > isotonic contraction —> weight not change, just length of while the load remains constant muscle change when tension stronger than load —> lift the load & muscle contract (isotonic contraction) lift down the load slowly —> increase length of muscle Concentric contraction – tension exceeds the (isotonic contraction); contraction rate low than load load; muscle shortening occurs retraction contraction Isometric Eccentric contraction – tension is smaller than the load; muscle extension occurs Cross-bridge cycle occurs in both isometric and isotonic contractions A combination of contraction types (e.g. archery) (https://open.oregonstate.education/aandp/chapter/10-4-nervous- system-control-of-muscle-tension/)  Sarcomere length-tension relationship Force (tension) generated by a stretch muscle —> downward relationship the longer the sarcomere length —> the less force generated muscle depends on the length of increase sarcomere length —> number of actin myosin interaction the muscle/sarcomere length of sarcomere decrease decrease (some of myosin head not touching each other) keep pulling apart —> less filament —> less room for actin contact point Optimal length (Lo) - the muscle myosin bind site —> less force —> less contact point —> less force generated length that develops the greatest tension Keeps by passive elasticity at Lo normal situation: muscle always proceed to during relaxation condition that generate maximum amount of force Decreased tension when deviates from Lo Sliding filament mechanism &increase number of motor unit involved —> increase muscle strength Whole muscles are made up of Control of muscle tension many myofibers organized into motor units Variable tension produced in response to different work needed Gradation of whole muscle tension E the tension in each myofiber; ① number of contracting myofibers Motor unit recruitment Process of increasing the no. of motor units Weak contraction – less motor units are activated small amount of force —> activate 1 motor unit want more force —> active more motor unit ② Number of myofibers per motor to increase strength —> increase muscle mass inse a e.g. 1 bigger muscle fiber can generate more force than 2 smaller fiber more room for myofibril ie unit varies [e.g. eye (~10) vs leg depends on type of activity of muscle (>1000)] muscle small motion for eyes —> precise movement —> involve more Finer control neuron per muscle fiber  Muscle twitch twitch = response of myofiber from contract to relax to contract Twitch – the mechanical response to a single AP (contraction and relaxation in a myogram) > with happens - no respond immediately Latent period – time for excitation- contraction coupling need time to induce Ca to bind to binding filament Contraction time – time interval from the a muscle cannot switch between fast and slow beginning of the tension development to genetically determined already the peak tension -contract/relx quickly Fast-twitch fiber vs slow-twitch fiber I general,a switch Y Duration of contraction - time that fromanother one to cytosolic Ca2+ remains elevated (i.e. Ca2+- ATPase activity) duration of contraction —> how long skeletal muscle contract —> time of Ca2+ not related to fast/slow twitch Twitch duration – time to complete their myosin —> slide microfilament —> cause contraction cross-bridge cycle (i.e. myosin type) stroke is quick —> fast twitch  Frequency-tension relationship Onset of contractile response (30 – 100 ms) lags behind the sustained contraction AP (1 – 2 ms) stimulus —> latent period —> release Ca2+ give stimulus before Twitch summation – increase —> myofiber contract muscle relax energy material used up in muscle tension from for lifting heavy weight successive action potentials Happens when a stimulus is high frequency of stimulus —> muscle has no time to relax applied before the completion —> keep peak contraction —> until meet the maximum force that of a twitch can be generated Fused tetanus – maintenance - of contraction sustained contraction More myosin-binding sites. remain available by persistent elevated Ca2+ Holding a heavy object in place, maintaining the posture  Muscle fatigue muscle contraction need ATP if not —> stop replenish not fast enough to replace usage Fatigue – inability to maintain muscle to P.17 · tension at a given level ATP is required for the power stroke, Ca2+ recycling, AP formation Muscle fatigue – depletion of muscle ATP, * Ca2+ leakage Ca2+ get into the cytoplamic reticulum —> need ATP ATP depleted —> cannot get in —> muscle cramp use Central fatigue – inadequately activates sliding model need relaxing muscle all need the motor neurons brain send signal to get rest protective mechanism Prevented by central fatigue happen first before total muscle fatigue limited amount can only be sustained in short period of time coordinated asynchronous recruitment diff of motor units 3 X need all motor units motor units > - use Recruitment of metabolically different alternatively foracertain is powerful muscle contraction from glucose to oxidative myofibers phosphorylation not enough usually will use glycolysis  Recruitment of motor unit contract longer time don’t need all motor unit activate all the time at one time only activate one before it drops —> activate another motor unit —> contract alternatively —> keep tension at high level but if want maximum power at short time —> activate all Asynchronous recruitment – some motor units contract when others start to relax. Produces continuous contraction of the whole muscle  Energy source during exercise for short time (few seconds) —> use ATP and energy store in creatine phosphate (limited amount) for longer time —> use muscle glycogen and glucose C fall twies muschs) for super long time (marathon) need long lasting substrate —> use free fatty acid Islow twites) misches change nutrient usage depends on exercise bc muscle has different types  Muscle fiber types ↓ Fox ↓Fg Skeletal muscle fibers do not have the same mechanical skeletal muscle has preference to use which substrate for energy source high abundance of IIx and metabolic characteristics slow —> oxidative phosphorylation (fatty acid) red in color —> have high amount of myoglobin (need oxygen for FA oxidation) seldom have only one type of muscle fiber type —> most of them mixed Slow-oxidative fast —> glycolysis (type I) fiber Fast-oxidative the twitch spedd faster than slow but use fatty acid instead of glycolysis (type IIa) fibers Fast-glycolytic high abundance of I and IIa slow oxidative (type IIx) fibers Velocity of shortening (Qaiser & Larsson Indian J Physiol Pharmacol 2014 58:1-12) Fast vs slow – myosin ATPase activity Pathway to form ATP fatty and - Oxidative (Red) vs glycolytic (White) – enzymatic machinery, (Pereyra et al Mol Metab 2022 59: 101456) mitochondria number, and amount of myoglobin fatigue resistance muscle —> can sustain for longer time cannot sustain long  Coordination of muscle type usage different types of skeletal muscle responsible for different type of activity erector muscle —> make body upright —> keep contracting all day long —> have more slow twitch bicep brachii —> lift for short period —> more fast twitch mostly determined by genetic but can change a little bit (adaptation) metabolic reprogramming —> change from IIx to IIa gl + 0X —> enhance endurance —> cannot change from fast to slow Most muscle contains a mixture of fiber types All the myofiber in a single motor units are of the same muscle type Differ in compositions (e.g. erector spinae vs bicep brachii) Genetics vs adaptation (transformation of fast-glycolytic to fast-oxidative)  Muscle cramping (www.basicphysiology.com) (https://krampade.com/our-science/) Muscle cramps - involuntary tetanic contraction due to high AP formation Sket muscles Painful contraction of a muscle or muscle group Uncertain cause Electrolyte imbalance in the extracellular fluid surrounding potassium level the muscle and nerve fiber do very prolonged period of exercise —> dehydration —> K lost by heavy sweating kidney will also draw in Na without K —> cramping (DK why yet) Caused by overexercise or persistent dehydration  spasm can be caused by Tetanus infection protein taken up by nerve Commonly known as “lockjaw” inhibit the inhibitory neuron (central fatigue mechanism) —> if blocked its activity —> motor neuron always be activated —> hyperactivity of the motor neuron muscle in jaw contracted —> cannot open mouth —> all muscle contracted Disease caused by a bacterial Tetanospasmin (Clostridium tetani) toxin via foreign body invasion Taken up by the inhibitory GABAergic and/or glycinergic neurons that control the activity of the lower motor neurons Hyperactivity of the motor neuron can develop breathing problem (which need relaxation) Muscle stiffness, breathing problems, and muscle spasms  Skeletal muscle and smooth similar in the way of contraction Cell shape muscle Cylindrical vs spindle Cell size 10 cm vs 50-400 μm Number of nuclei Multinucleated vs single nuclear Functional units Sarcomere vs network sense (at paper fase - Microfilament composition thick similar thin no Myosin, troponin, and tropomyosin vs myosin and - summe the un tropomyosin , (X troponin) -> cannot sense Can Microfilament arrangement Parallel myofibril vs diagonally from side to side Shapes change after contraction Shorten length vs bulges out between dense body Neuronal control (https://www.brainkart.com/article/Smooth-Muscle-and-Cardiac-Muscle_21797/) NMJ vs varicosities  Organization of muscle cells Layer of muscle cells Bundle of myofiber organized in sheet —> surround the organ Skeletal muscle and smooth muscle (https://onlinelibrary.wiley.com/doi/10.1111/asj.13226) Dense body both need Ca to contract don’t contain troponin which sense Ca2+ to stop the muscle contraction stop by other mechanism Skeletal muscle and smooth muscle contraction Z-line Z-line  Cross-bridge cycle in smooth muscle Myosin-actin interaction is not physically but chemically blocked Phosphorylation on the myosin Relaxation is Troponin accomplished by the removal of ADP ADP Ca2+ Pi Pi CaM: Calmodulin MLCK: myosin light chain kinase  Neuronal control of smooth muscle contraction Contractile activity is controlled by neurotransmitters from the autonomic neuron Varicosities swollen regions in the branched neuron ending Vesicles filled with neurotransmitter Enhances or decreases contractile activity Same neurotransmitter might induce different responses, e.g. Epi in blood vessels and in bronchiolar muscle  Types of smooth muscles Single-unit smooth muscle Multiunit smooth muscle Response to stimulation as a whole Response independently Linked by gap junctions Highly innervated by autonomic nerve Propagation of electric signals Total contraction depends on the number of activated Contractile activity can be induced by cells and frequency of nerve stimulation stretching Finer control Digestive organs Arteries, bronchi, eye After the lecture, you should be able to explain Anatomical differences between different muscles Classification of myofibers Regulation of muscle contraction Mechanism of muscle contraction Factors that control force generation