THE MUSCULAR SYSTEM: SKELETAL MUSCLE TISSUE AND MUSCLE

THE MUSCULAR SYSTEM: SKELETAL MUSCLE TISSUE AND MUSCLE

THE MUSCULAR SYSTEM: SKELETAL MUSCLE TISSUE AND MUSCLE ORGANIZATION 3 Types of Muscle Tissue Skeletal muscle attaches to bone, skin or fascia striated with light & dark bands visible with scope voluntary control of contraction & relaxation 3 Types of Muscle Tissue Cardiac muscle striated in appearance involuntary control autorhythmic because of built in pacemaker 3 Types of Muscle Tissue

Smooth muscle attached to hair follicles in skin in walls of hollow organs -- blood vessels & GI nonstriated in appearance involuntary Muscle Tissue: Functions 1. producing body movements integrated action of skeletal muscle, joints and bones 2. stabilizing body positions skeletal muscle contraction stabilizes joints and bones postural muscles contract continuously when awake

3. maintain body temperature 4. storing and moving substances in the body contraction of ring-like smooth muscle sphincters storage of material in an organ regulation of entrance and exit to and from the body storage of glucose within skeletal muscle movement of blood by cardiac muscle and by smooth muscle within the blood vessels movement of food through the GI tract by smooth muscles within abdominal viscera born with a predetermined number of skeletal muscle cells can be replaced if damaged or old = muscle stem cells muscle fibers increase in size during childhood = human GH testosterone also increases muscle size mature muscle fibers range from 10 to 100 microns in diameter

typical length is 4 inches - some are 12 inches long Properties of Skeletal Muscles Electrical excitability -ability to respond to stimuli by producing electrical signals such as action potentials -two types of stimuli: 1. autorhythmic electrical signals 2. chemical stimuli Contractility -ability to contract when stimulated by an AP -isometric contraction: tension develops, length doesnt change -isotonic contraction: tension develops, muscle shortens Extensibility -ability to stretch without being damaged -allows contraction even when stretched Elasticity -ability to return to its original length and shape

Gross Anatomy muscles are really groups of fascicles the fascicles are groups of muscle fibers = considered to be an individual muscle cell muscles are covered superficially by a superficial fascia layer (or subcutaneous layer) three layers of connective tissue extend from a deep fascial layer to segment the muslce into bundles

these layers further strengthen and protect muscle outermost layer = epimysium Epimysium Perimysium Endomysium encircles the entire muscle next layer = perimysium

surrounds groups of 10 to 100 individual muscle fibers separates them into bundles = fascicles give meat its grain because the fascicles are visible both epimysium and perimysium are dense irregular connective tissue penetrating the fasicles and separating them into individual muscle fibers = endomysium (areolar connective tissue) all three of these connective tissue layers extend beyond the muscle and attaches it to other structures -called a tendon = cord of regular dense CT that attaches a muscle to the periosteum of bone the muscle fiber is made up of fused muscle cells -these muscle cells have a unique cytoskeleton

made up of myofibrils each myofibril is comprised of repeating units of protein filaments = sarcomeres The muscle cell: contents Plasma membrane = sarcolemma nuclei organelles golgi, lyososome mitochondria sarcoplasmic reticulum T-tubules

Cytoplasm = sarcoplasm cytoskeleton microtubules intermediate filaments (desmin) actin myosin other structural proteins cytosol

water ions glycogen (glucose) myoglobin (oxygen) creatine phosphate (ATP) Microanatomy of Skeletal Muscle Fibers New terminology Cell membrane = sarcolemma Cytoplasm = sarcoplasm Internal membrane system = sarcoplasmic reticulum

Muscle Cell Anatomy Transverse tubules Connect to sarcolemma Carry electrical impulses/APs Myofibrils within sarcoplasm Protein filaments organized as Sarcomeres Myofibrils made of myofilaments Thin filaments (actin, troponin, tropomyosin) Thick filaments (myosin) Microanatomy of Skeletal Muscle Fibers muscle fibers are bound by a plasma membrane = sarcolemma

thousands of tiny invaginations in this sarcolemma called T or transverse tubules - tunnel in toward the center of the cell -T tubules are open to the outside of the fiber - continuous with the sarcolemma - filled with interstitial fluids action potentials travel along the sarcolemma and the T tubules - allows for the even and quick spread of an action potential the cytoplasm is called a sarcoplasm -substantial amounts of glycogen - can be broken into glucose -contains myoglobin - binds oxygen needed for muscle ATP production Microanatomy of Skeletal Muscle Fibers contractile elements of the muscle fibrils = myofilaments -2 microns in diameter -comprised of actin or myosin -give the muscle its striated appearance

fibers have a system of fluid-filled membranes = sarcoplasmic reticulum -encircles each myofibril -similar to the ER -have dilated end sacs = terminal cisterns -stores calcium when at rest - releases it during contraction -release is triggered by an AP Muscle development Large, multinucleated cells embryonic development - muscle fibers arise from fusion of a hundred or more mesodermal cells called myoblasts organized into muscle fibers composed of myofibrils once fused, these muscle cells lose the ability of undergo mitosis - number of muscle cells predetermined before birth myoblasts develop from stem cells

adult these stem cells are called satellite cells also can come from bone marrow stem cells? M line Sarcomere Structure sarcomere = regions of myosin (thick myofilament) and actin (part of thin myofilament) bounded by the Z line thin filaments project out from Z line actin attaches via actinin (structural protein) thick filaments lie in center of sarcomere - overlap with thin filaments and connect to them via cross-bridges myosin/thick filament only region = H zone myosin/thick filaments are held in place by the M line proteins at the center and titin at the Z-line thin filament only region = I band length of myosin/thick filaments = A band

contraction = sliding filament theory -thick and thin myofilaments slide over each other and sarcomere shortens Sarcomere structure I band region of thin filaments only split in half by the Z line Z line denotes the sarcomere comprised of proteins called connectins (e.g. actinin) that interconnect the thin filaments from sarcomere to sarcomere also connect to a structural protein called titin keeps thick and thin filaments in proper alignment and resists extreme stretching forces connected to adjacent myofibrils by intermediate filaments (e.g. desmin) results in the sarcomeres from adjacent myofibrils aligning with each other = striated appearance

M line made up of a protein called the M line protein binds an enzyme for ATP storage called creatine kinase helps in the positioning of the thick filaments between the thin filaments A band length of the thick filament contains the zone of overlap between thin and thick filaments The Proteins of Muscle Myofibrils contain two kinds of myofilaments Thin Thick

Myofibrils are built of 3 kinds of protein contractile proteins myosin and actin regulatory proteins which turn contraction on & off troponin and tropomyosin structural proteins which provide proper alignment, elasticity and extensibility titin, myomesin, nebulin and dystrophin

Structural proteins of muscle Nebulin, an inelastic protein helps align the thin filaments. Dystrophin links thin filaments to sarcolemma and transmits the tension generated to the tendon. Titin anchors thick filament to the M line and the Z line. -the portion of the molecule between the Z line and the end of the thick filament can stretch to 4 times its resting length and spring back unharmed. -has a role in recovery of the muscle from being stretched.

Contractile proteins of muscle: Actin two forms of actin G-actin and F-actin the G-actin beads are assembled together (using ATP) to form two linear chains of actin called F-actin these two chains are wrapped around a core rod of nebulin to form a helix F-actin filament is associated with the regulatory proteins troponin and tropomyosin the myosin-binding site on each actin bead is covered by tropomyosin in relaxed muscle Contractile proteins of muscle: Myosin myosin thick myofilament is a bundle of myosin molecules each myosin protein is made up of two heavy chains each with a globular head with a site to bind ATP and a site to bind actin also associated with the heads are 4 light chains play a role in myosins assembly and ability to hydrolyze ATP

Contraction: The Sliding Filament Theory Contraction: Active process Elongation is passive Amount of tension produced is proportional to degree of overlap of thick and thin filaments SF Theory: Explains how a muscle fiber exerts tension Four step process Active sites on actin Crossbridge formation

Cycle of attach, pivot, detach, return Troponin and tropomyosin control contraction RESETTING of system Increase in Cai Removal of troponin-tropomyosin CONTRACTION Sliding of actin along myosin -for cross bridging- you will need two things: 1. calcium uncovers the myosin binding sites on actin pushes aside the troponintropomyosin complex 2. myosin head bound to ADP -for contraction i.e. pivoting of the myosin head into the M line the myosin head must be empty -to reset for a new cycle of cross-bridging the myosin head must detach and pivot back -the myosin head must bind ATP

-once the myosin head pivots back the ATP is broken down to ADP head is ready to crossbridge again if actin is ready CHECK OUT THIS ANIMATION!!! http://www.blackwellpublishing.com/ matthews/myosin.html Sarcoplasmic Reticulum and Calcium release the SR wraps around each A and I band segmented with T-tubules between each SR segment

each segment forms saclike regions at the ends = lateral sacs on the lateral sac of the SR is an orderly arrangement of proteins = foot proteins (ryanodine receptors) these foot proteins bridge the gap between SR and T-tubule serve as Ca release channels 50% of the foot proteins of the SR are zipped together with similar proteins found on the T-tubule (dihydropyridine receptors) the T-tubule receptors respond to changes in voltage voltage-gated sensors when an AP travels down the T-tubule the local depolarization activates these sensors which then open the foot proteins on the SR the opening of these foot proteins triggers the SR to open the remaining foot proteins that are not connected to the T-tubule efflux of calcium into the sarcoplasm The Neuromuscular Junction end of neuron (synaptic terminal or axon bulb) is in very close association

with a single muscle fiber (cell) nerve impulse leads to release of neurotransmitter (acetylcholine) from the synaptic end terminal AcH binds to receptors on myofibril surface (ligand-gated Na channels) binding leads to influx of sodium ions and depolarization of the membrane potential of the sarcolemma creation of an action potential that travels through the muscle cell eventual contraction Acetylcholinesterase breaks down ACh Limits duration of contraction Muscle Contraction: A summary

called excitation-contraction coupling describes the events linking generation of an AP (excitation) to the contraction of the muscle ACh released from synaptic vesicles at each neuromuscular junction Binding of ACh to motor end plate (muscle cell of the NMJ) entrance of Na ions and depolarization Generation of electrical impulse in sarcolemma action potential Conduction of impulse along T-tubules AP flows along the outside of the muscle cell via the sarcolamma

also enters the inside of the muscle cell via T-tubules close association of T-tubules with the sarcoplasmic reticulum (SR) Release of Calcium ions by SR AP results in release of Ca by the SR SR is in close physical association with each A and I band Ca binds to troponin and pulls it away from the actin filament Exposure of active sites on actin Cross-bridge formation with myosin Formation of ATP by the muscle cell sliding filaments & contraction

The Events in Muscle Contraction CHECK OUT THIS ANIMATION!!! http://www.blackwellpublishing.com/ matthews/myosin.html Relaxation Acetylcholinesterase (AChE) breaks down ACh within the synaptic cleft Muscle action potential ceases Ca+2 release channels (foot proteins) close Active transport pumps Ca2+ back into storage in the sarcoplasmic reticulum Ca ATPase pumps the rate of pumping Ca back into the SR is slower than the rate of efflux so as long as the muscle is being stimulated via the T-tubules more Ca in

the sarcoplasm Calcium-binding protein (calsequestrin) helps hold Ca+2 in SR enables more calcium to be stored in the SR calcium concentration is 10,000 more concentrated in the SR than in the sarcoplasm Tropomyosin-troponin complex recovers binding site on the actin Rigor Mortis Rigor mortis is a state of muscular rigidity that begins 3-4 hours after death and lasts about 24 hours After death, Ca+2 ions leak out of the SR and allow myosin heads to bind to actin Since ATP synthesis has ceased, crossbridges cannot detach from actin until proteolytic enzymes begin to digest the

decomposing cells. Length of Muscle Fibers: Length Tension relationship Normally Optimal overlap of thick & thin filaments

produces greatest number of crossbridges and the greatest amount of tension optimal length = lo (muscle length at which maximum force is generated) optimal length = point A As stretch muscle (past optimal length) length of the muscle fiber is greater than lo fewer cross bridges exist & less force is produced = point B when muscle is stretched to about 70% than lo of its (point C) the actin filaments are completely pulled out from between the myosin no cross-bridges possible

resting muscle length remains between 70 to 130% of the optimum If muscle is overly shortened (less than optimal) length of the muscle fiber is less than lo thick filaments crumpled by Z discs and the actin filaments overlap poor cross-bridge formation fewer cross bridges exist & less force is produced =

point D even less calcium released from the SR - ?? A B D C Levers Motor Units

Each skeletal fiber has only ONE NMJ MU = Somatic neuron + all the skeletal muscle fibers it innervates Number and size indicate precision of muscle control Muscle twitch Single momentary contraction in one muscle fiber too small to generate any significant force Response to a single stimulus

All-or-none theory Either contracts completely or not at all Motor units are grouped together to provide a greater force in a whole muscle fire asynchronously -some fibers are active others are relaxed -delays muscle fatigue so contraction can be sustained Muscle fibers of different motor units are intermingled so that net distribution of force applied to the tendon remains constant even when individual muscle groups cycle between contraction and relaxation. Neural control of Motor Units 1. input from afferent neurons

at the level of the SC by interneurons within the SC = spinal reflex afferent information is needed to control skeletal muscle activity the CNS must know the position of your body prior to initiating movement and must know how the movement is progressing = prioprioceptive input comes from information from your eyes, joints, inner ear and from the muscles themselves (prioprioceptors) muscle spindles and tendon organs within the muscle monitor changes in muscle length and tension (see lecture 9) 2. input from the motor cortex fibers originating from neuronal cell bodies within the primary motor cortex = pyramidal cells descend directly (as one continuous axon) to synapse with motor neurons in the SC

part of the corticospinal motor system (lecture 8) 3. input from the brain stem extrapyramidal motor system involves many regions of the brain final link is the brain stem 1. muscle spindles monitor changes in muscle length used by the brain to set an overall level of involuntary muscle contraction = motor tone consists of several sensory nerve endings that wrap around specialized muscle fibers = intrafusal muscle fibers very plentiful in muscles that produce very fine movements

fingers, eyes stretching of the muscle stretches the intrafusal fibers, stimulating the sensory neurons info to the CNS IFMs also receive incoming information from gamma motor neurons end near the IFMs and adjust the tension in a muscle spindle according to the CNS also have extrafusal muscle fibers which are innervated by alpha motor neurons response to a stretch reflex 2. tendon organs located at the junction of a tendon and a

muscle protect the tendon and muscles from damage due to excessive tension consists of a thin capsule of connective tissue enclosing a few bundles of collagen penetrated by sensory nerve endings that intertwine among the collagen fibers Motor Tone Resting muscle contracts random motor units Constant tension created on tendon Resting tension muscle tone Stabilizes bones and joints Muscle Metabolism

Production of ATP: -contraction requires huge amounts of ATP -muscle fibers produce ATP three ways: 1. Creatine phosphate 2. Aerobic metabolism 3. Anaerobic metabolism Creatine Phosphate Muscle fibers at rest produce more ATP then they need for resting metabolism Excess ATP within resting muscle used to form creatine phosphate or phosphocreatine

Creatine phosphate: 3-6 times more plentiful than ATP within muscle the first storehouse of energy used upon the onset of contraction when additional ATP is needed Its quick breakdown provides energy for creation of ATP Sustains maximal contraction for 15 sec (used for 100 meter dash) or about 8 muscle twitches creatine phosphate breakdown is favored by muscles undergoing explosive movements Athletes tried creatine supplementation gain muscle mass but shut down bodies own synthesis (safety?) Aerobic Cellular Respiration

Muscles deplete creatine make ATP in anaerobically or aerobically aerobic respiration produces ATP for any activity lasting over 30 seconds Provides 90% of ATP energy if activity lasts more than 10 minutes must be moderate activity if sufficient oxygen is available, pyruvic acid enters the mitochondria to generate ATP, water and heat via the electron transport chain fatty acids and amino acids can also be used by the mitochondria

moderate activities like walking O2 levels must be sufficient!!!!! Each glucose = 36 ATP Fatty acids = ~100 ATP Sources of oxygen diffusion from blood, released by myoglobin (hemoglobin-like molecule of muscle cells) Anaerobic Cellular Respiration Muscles deplete creatine make ATP in anaerobically via glycolysis only Glycogen converted into glucose

normally ATP produced from the breakdown of glucose into pyruvic acid during glycolysis and this enters the citric acid cycle and electron transport chain to make ATP if insufficient oxygen is present glycolysis creates the products for oxidative phosphorylation glucose is broken down into two pyruvic acid molecules to yield 2 ATP BUT in low oxygen this pyruvic acid is further processed to yield more ATP by-product = lactic acid Glycolysis can continue anaerobically to provide ATP for 30 to 40 seconds of maximal activity (200 meter race)

http://www.indstate.edu/thcme/mwking/oxidative-phosphorylation.html Muscle Fatigue Inability to contract after prolonged activity central and peripheral fatigue central fatigue is feeling of tiredness and a desire to stop (protective mechanism) Factors that contribute to muscle fatigue

depletion of creatine phosphate decline of Ca+2 within the sarcoplasm insufficient oxygen or glycogen accumulation of extracellular K ions drop in pH within muscle cell buildup of lactic acid buildup of ADP and inorganic phosphate from ATP hydrolysis insufficient release of acetylcholine from motor neurons Isotonic and Isometric Contraction Isotonic contractions = a load is moved concentric contraction = a muscle shortens to produce force and movement eccentric contractions = a muscle lengthens while maintaining force and movement

Isometric contraction = no movement occurs tension is generated without muscle shortening maintaining posture & supports objects in a fixed position Atrophy wasting away of muscles caused by disuse (disuse atrophy) or severing of the nerve supply (denervation atrophy) the transition to connective tissue can not be reversed Hypertrophy increase in the diameter of muscle fibers resulting from very forceful, repetitive muscular activity and an increase in myofibrils, SR & mitochondria Exercise-Induced Muscle Damage Intense exercise can cause muscle damage

electron micrographs reveal torn sarcolemmas, damaged myofibrils an disrupted Z discs increased blood levels of myoglobin & creatine phosphate found only inside muscle cells Delayed onset muscle soreness 12 to 48 Hours after strenuous exercise stiffness, tenderness and swelling due to microscopic cell damage Three Types of Muscle Fibers Fast fibers = glycolytic Slow fibers = oxidative 10 times slower than fast fibers Intermediate fibers Fibers of one motor unit all the same type Percentage of fast versus slow fibers is genetically

determined Proportions vary with the usual action of the muscle - neck, back and leg muscles have a higher proportion of postural, slow oxidative fibers - shoulder and arm muscles have a higher proportion of fast glycolytic fibers Fast Fibers Large in diameter Contain densely packed myofibrils Large glycogen reserves high ATPase activity faster cross-bridge potential

Fast oxidative (fast-twitch A) (intermediate fibers) red in color (lots of mitochondria, myoglobin & blood vessels) higher ability to produce ATP via aerobic metabolism highly vascularized split ATP at very fast rate; used for walking and sprinting Fast glycolytic (fast-twitch B)

white in color (few mitochondria & BV, low myoglobin) higher concentration of enzymes for glycolysis need less oxygen to function anaerobic movements for short duration; used for weight-lifting low resistance to fatigue Slow fibers Half the diameter of fast fibers Three times longer to contract low ATPase activity, low glycogen content high resistance to fatigue higher ability to produce ATP via aerobic metabolism many mitochondria

highly vascularized Continue to contract for long periods of time e.g. marathon runners Muscle Adaptation long-term adaptive changes can occur with exercise depending on the pattern of neuronal discharge 1. improvement of oxidative capacity regular aerobic activity induces metabolic changes in the oxidative fibers increases number of mitochondria and capillaries to the fast and slow oxidative fibers more efficient use of oxygen prolonged activity without fatigue 2. muscle hypertrophy increased by regular bursts of short, anaerobic, high-intensity exercise increases the diameter of the muscle fiber increase synthesis of myosin and actin

exercise triggers the activation of specific genes that direct the synthesis of actin and myosin also a role for muscle stem cells? 3. influence of testosterone makes muscle fibers thicker promotes the synthesis of myosin and actin Smooth muscle slowest of contraction and relaxation of all three types of muscle lowest O2 consumption rates require less energy to contract generates force over longer periods of time maximum tension with only 25-30% of cross-bridges active can still generate tension even when over-stretched the nonstretched length of smooth muscle is shorter than skeletal

therefore it can be stretched quite a distance before the optimal length is reached important for the contractile ability of hollow organs and blood vessels Characteristics of Smooth Muscle have more variety with differing properties vascular, gastrointestinal, urinary, respiratory, reproductive, ocular single model of smooth muscle function is impossible anatomy is distinct fibers are arranged in oblique bundles (lattice-like) so that contractile forces are generated in multiple directions also several organs have multiple layers of SM

contraction is controlled by hormones, paracrines and NTs ACh, NE, Epi etc variable electrical properties do NOT always respond to an AP with a twitch some can hyperpolarize in response others can contract without reaching threshold!! Smooth muscle three filaments: myosin, actin and intermediate sized filaments (dont participate in contraction) forms of actin, myosin are specific to smooth muscle more actin vs. skeletal muscle express tropomyosin only

have no sarcomeric structure do not have Z lines the actin and myosin filaments are organized in a lattice-like pattern rather than parallel to each other have dense bodies same proteins as found in Z lines positioned throughout the cell and attach to the internal surface of the PM held in place by the cytoskeleton of the cell act as an anchor for actin filaments

no T-tubule structure and poorly developed sarcoplasmic reticulum neural excitation differs from skeletal muscle cells AP travels along the PM of the smooth muscle cell opens calcium channels in the PM flows in from the ECF this increased calcium from the ECF triggers the opening of ryanodine Ca receptors on the SR these act as calcium channels also can still generate tension even when over-stretched the nonstretched length of smooth muscle is shorter than skeletal therefore it can be stretched quite a distance before the optimal length is reached important for the contractile ability of hollow organs and blood vessels turned on by calcium-dependent phosphorylation of myosin

since there is no troponin how does the cell prevent cross-bridge formation at rest? lightweight chains of proteins myosin light chain proteins attach to the head of myosin increasing cytosolic calcium initiates a series of biochemical events that phosphorylates the myosin light chain this allows an interaction between actin and myosin so there is two forms of myosin in muscle cells (skeletal too!) myosin heavy and myosin light myosin light chains have no function in skeletal muscle contraction Smooth muscle contraction: A summary influx of calcium into cell multiple ways of doing this increase in cytosolic Ca levels multiple ways of doing this also dramatic increase in calcium activates a calcium-dependent

kinase = calmodulin/CaM CaM activates another kinase called CaM kinase/CaMK CaMK activates another kinase = myosin light chain kinase/MLCK phosphorylation of myosin light chain by MLCK phosphorylation allows crossbridging to actin this phosphorylation also increases the ATPase activity of the myosin on the head of the myosin heavy chain increased ATPase activity allows for myosin head pivoting and contraction is generated Smooth muscle organized as multi-unit or single-unit smooth muscles multi-unit exhibits neural-like properties muscle fibers within the muscle contract as a unit multiple units per muscle each unit is stimulated by nerves to contract similar to skeletal muscle

motor units so multi-unit smooth muscle is neurogenic nerve produced supplied by the ANS single unit self-excitable muscle fibers within the muscle contract as a separate, single unit found in cell walls of organs and blood vessels cells are linked by gap junctions for spread of AP interconnected cells form a functional syncytium myogenic self excitable some cells are stimulated through opening of mechanically-gated calcium channels stretch-activated

clusters of cells exhibit spontaneous electrical activity without neural stimulation clusters are specialized to initiate an AP BUT are not specialized to contract their membrane potential fluctuates automatically without any external influence two type of spontaneous depolarizations: pacemaker and slowwave potentials slow wave exhibit cyclic depolarization and repolarization might not reach the threshold level and might not contract pacemaker always reach their threshold potential create regular rhythms of contraction and relaxation

Smooth muscle: Myogenic smooth muscle tone: single-unit smooth muscle interconnection ensures that the entire muscle contracts upon initiation of an AP by a unit cant vary the number of muscle fibers contracting BUT can vary the tension varying the cytosolic calcium can alter the number of eventual crossbridges that form alters strength of contraction many single units have sufficient calcium within their cytosol to ensure a low level of constant contraction = tone smooth muscle activity: innervated by the ANS does not initiate the contraction but modifies the rate and strength of contraction of single-unit smooth muscle also can be modified by: hormones, muscle stretch, drugs all act by modifying the permeability of the PM to calcium in the ECF

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