Muscles & Physiology I

Collin College BIOL 2401 Muscles & Physiology I 1 TYPES OF MUSCLE Cardiac muscle heart muscle tissue striated but involuntary includes a pacemaker system that causes the heart to beat Smooth Muscle located in the walls of hallow internal structures non-striated (therefore appears as "smooth" ) involuntary Skeletal muscle attached primarily to bone striated voluntary 2 1

TYPES OF MUSCLE 3 FUNCTION OF MUSCLE Produces motion involved in the integrated functioning and movement of bones and joints via skeletal muscle less noticeable is the motion of the heart and that of the internal organs such as gut Maintain posture Stabilizes joints Supports soft tissues and Regulates organ volume Generates heat : muscle contraction generates 80-85 % of body heat 4 2

CHARACTERISTICS OF MUSCLE Excitability : ability to respond to stimuli (chemical) by producing electrical signals (current) Contractility : ability to shorten and thicken (contract), thereby producing force Extensibility : ability to stretch without damage to the tissue (opposing muscle is always stretched when primary muscle contracts) Elasticity: ability to return to its original length and shape after being stretched 5 CHARACTERISTICS OF MUSCLE Skeletal muscles attach to bones across joints Skeletal muscles are organized in agonistic/ antagonistic pairs. A muscle can shorten and pull on a bone, but cannot push a bone away. 6 3

CHARACTERISTICS OF MUSCLE Prefix Terminology with respect to muscles. Myo - : refers to muscle myo-cyte myo-fillament Sarco - : means flesh used in for example sarcolemma sarcoplasma sarcoplamic reticulum Cardio - : refers to the heart 7 Anatomy of Skeletal Muscle Skeletal muscles are attached to the skeleton by tendons. A muscle bundle is made out of groups containing many individual muscle cells. Such groups are called fascicles. A single muscle cell is called a muscle fiber. 8 4

Anatomy of Skeletal Muscle Three layers of connective tissue are part of each muscle. Epimysium : surrounds the whole muscle made from dense regular CT Perimysium surrounds the muscle fascicles contains collagen/elastic fibers Also holds the blood vessels and nerves Endomysium surrounds each muscle fiber made from areolar CT contains capillaries and myosatellite celsl At the end of the muscle, the 3 C.T. tissues come together and form a tendon or an aponeuris (broad tendon sheet). 9 a Skeletal Muscle (organ) Epimysium Perimysium Endomysium Nerve Muscle fascicle Muscle fibers Blood vessels Bone Epimysium Blood vessels and nerves Tendon Endomysium Perimysium 10 10 5

Anatomy of Skeletal Muscle Bone Tendon Epimysium (b) Blood vessel Epimysium Perimysium Endomysium Muscle fiber in middle of a fascicle Fascicle (wrapped by perimysium) Endomysium (between individual muscle fibers) Perimysium (a) Fascicle Muscle fiber 11 Anatomy of Skeletal Muscle Each muscle is served by one nerve, an artery, and one or more veins Each skeletal muscle fiber is supplied with a nerve ending that controls contraction Contracting fibers require continuous delivery of oxygen and nutrients via arteries Wastes must be removed via veins 12 6

Skeletal Muscle Fibers (cells) Muscle cells originate from the fusion of embryonic cells called myoblasts. Each cell is thus a syncytium produced by fusion of embryonic cells They are thus multinucleate are in general slender and long ( 100 um wide, sometimes 12 inches long) Satellite cells are unfused myoblast cells that remain active in assisting the regeneration of damaged muscle fibers 13 Skeletal Muscle Fibers (cells) 14 7

Skeletal Muscle Fibers (cells) Each muscle fiber (cell) is a long, cylindrical cell with multiple nuclei just beneath the sarcolemma Fibers are 10 to 100 mm in diameter, and up to hundreds of centimeters long Sarcoplasm has numerous glycosomes (glycogen containing bodies) and a unique oxygen-binding protein called myoglobin Fibers contain the usual organelles such as mitochondria, sarcoplasmic reticulum and special structures called myofibrils and T tubules. 15 Micro-Anatomy of Skeletal Muscle Each skeletal muscle fascicle is typically composed of many muscle fibers (cells). Each muscle fiber (=muscle cell) is packed with long cylindrical myofibrils. Each myofibril in turn is made out of smaller protein based structures called myofilaments. The myofilaments are organized into sarcomeres, which are the contractile units of a muscle cell. 16 8

Micro-Anatomy of Skeletal Muscle 17 MyoFibrils Muscle cell Sarcolemma Mitochondrion Dark A band Light I band Nucleus Myofibril Myofibrils are densely packed, rodlike contractile elements They make up most of the muscle volume The arrangement of myofibrils within a fiber is such that a perfectly aligned repeating series of dark bands (the A bands) and light bands (the I bands) are evident 18 9

Myofibrils & Myofilaments Each myofibril is made from bundles of proteins called the myofilaments. There are two major proteins involved : Actin : they form the thin filaments Myosin : they form the thick filaments These proteins within the myofibrils are the actual contractile elements of a muscle 19 Sarcomeres Myofibril Each myofibril is made up of around 1000 s of sarcomeres arranged in series (back to back) The sarcomere is smallest contractile unit of a muscle The region of a myofibril between two successive Z discs Composed of myofilaments made up of the contractile proteins actin, mysosin and other proteins. 20 10

Sarcomeres : the unit of contraction Thick filaments: run the entire length of an A band Thin filaments: run the length of the I band and partway into the A band Z disc: coin-shaped sheet of proteins that anchors the thin filaments and connects myofibrils to one another H zone: lighter midregion where filaments do not overlap M line: line of protein myomesin that holds adjacent thick filaments together Elastic bands (made from titin protein) attach thick filamansts to z-discs 21 Sarcomeres : the unit of contraction Thin (actin) filament Z disc H zone Z disc Thick (myosin) filament I band A band Sarcomere I band M line (c) Small part of one myofibril enlarged to show the myofilaments responsible for the banding pattern. Each sarcomere extends from one Z disc to the next. Z disc Sarcomere M line Z disc Thin (actin) filament Elastic (titin) filaments Thick (myosin) filament (d) Enlargement of one sarcomere (sectioned lengthwise). Notice the myosin heads on the thick filaments. 22 11

Sarcomeres : the unit of contraction I band A band H band Z line Titin Zone of overlap M line Sarcomere Thin Thick filament filament a I bands have only thin filaments. A bands have both thin and thick filaments. H bands have thick filaments and bisect A bands. M lines are the middle of H bands. Z lines bisect the I bands. 23 Skeletal Muscle Surrounded by: Epimysium Contains: Muscle fascicles Myofibril Surrounded by: Sarcoplasmic reticulum Consists of: Sarcomeres (Z line to Z line) Sarcomere I band A band Muscle Fascicle Contains: Thick filaments Surrounded by: Perimysium Thin filaments Contains: Muscle fibers Z line M line Z line Titin H band Muscle Fiber Surrounded by: Endomysium Contains: Myofibrils 24 12

Structure of Thin Filaments The thin filament (F-actin) called actin is a polymer of G-actin protein molecules. Each G-actin molecule has a binding site to which a myosin head can bind 25 Structure of Thin Filaments The binding sites on actin are covered by a tropomyosin filament. The tropomyosin filament is attached to the actin chain by means of a Troponin complex. 26 13

Structure of Thin Filaments In relaxed skeletal muscle, tropomyosin blocks the myosin head (also called cross-bridge) binding site on actin. When calcium ions bind to troponin, the troponin complex pulls tropomyosin away from the cross-bridge binding site. This allows myosin cross-bridges to attach to actin and is at the basis of muscle contraction. 27 Structure of Thick Filaments Titin c The structure of thick filaments, showing the orientation of the myosin molecules M line d Myosin tail Hinge The structure of a myosin molecule Myosin head The thick filament called myosin is actually a polymer of myosin molecules Each has a flexible cross-bridge (head) with ATPase activity and with a binding site for actin. 28 28 14

Structure of Sarcomore & Filaments Myosin head 29 Structure of Myofibril and Sarcomere Each thick filament is surrounded in a hexagonal pattern by 6 thin filaments. 30 15

Sarcolemma and Skeletal Muscle The cell membrane of a Skeletal muscle is called sarcolemma It is an excitable membrane ; has similar properties as a nerve cell membrane Has a resting membrane potential Has the ability to generate action potentials along that membrane (what does this implicate? ) IN nerve tissue, the purpose of the action potential is guide the electrical activity towards the axon terminal end-point, where it results in the release of Neurotransmitters! The purpose of the action potential on a muscle cell is to start the process of contraction. 31 T-tubules and SarcoPlasmic Reticulum Skeletal Muscle contraction is started by the release of calcium from the internal stores, the Sarcoplasmic Reticulum (SR) Problem : SR is located within the cell and Action Potentials run along the plasma-membrane! - - - - - - + + + + Act. Pot. Motor neuron S.R Contains [Ca 2+ ] 32 16

T-tubules and Sarcolemma The action potential has to be guided to the inside of the cell so it can reach out and touch the SR. S.R Contains [Ca 2+ ] This is accomplished by narrow membrane pits, tubular extension of the plasma membrane that extend deep within the sarcoplasma. These are called the T-tubules! 33 T-tubules and SarcoPlasmic Reticulum T-tubules dip into the cell at the Z-discs Smooth endoplasmic reticulum of a muscle cell = sarcoplasmic reticulum encircles each myofirbril of the cell with interconnecting tubules that run longitudinally Thus, each sarcomere has a source of calcium close by Myofibril Mitochondria Sarcolemma Thin filament Thick filament Triad Sarcoplasmic reticulum T tubules Ter minal cisterna Sarcolemma Sarcoplasm Myofibrils 34 17

T-tubules and Sarcolemma Interconnecting sacs of the SR run on either side of the T-tubules = terminal cisternae or end sacs Combination of T-tubules and a pair of surrounding terminal cisternes = Triad system Calcium is released from the SR via special Calcium-release channels that 35 respond to a voltage change Aspect of Contraction Contraction of a muscle fiber Occurs when the myosin heads latch on to the actin filament The cross bridges then pull forward This causes the actin filaments to slide inwards and to pull the z-line towards each other This sliding results in the sarcomere to shorten without altering the length of actin or myosin filaments Called the sliding filament theory 36 18

Aspect of Contraction During Contraction thick and thin filaments do not shorten! THEY SLIDE OVER EACH OTHER. The sarcomere shortens The A bind remains the same size - The I band shortens A band I band 37 Aspect of Contraction Requirements for Skeletal Muscle Contraction 1. Activation = neural stimulation via motor neuron and release of N.T. at a neuromuscular junction 2. Excitation-contraction coupling: Generation and propagation of an action potential along the sarcolemma Final trigger: a brief rise in intracellular Ca 2+ levels via release from the Sarcoplasmic Reticulum 38 19

NeuroMuscular Junction Area where somatic motor neuron (axon) and skeletal muscle cells make contact The motor end plate is the surface of the muscle cell where the synapse occurs. As a rule, each muscle fiber (cell) has only one NMJ but one motor neuron can activate many cells via collateral branches. Synapse is between the motor neuron axon on one side and the motor endplate on the other side ACh is the neurotransmitter and the motor endplate carries ACh receptors 39 Events at NMJ Release of ACh is triggered by an AP and results in opening of voltage gated Ca-channels in the axon terminal of the motor neuron. Binding of ACh at the motor endplate opens up chemically gated Na-channels (nicotinic ACh receptor) This triggers a local de-polarization (graded potential) that reaches outside of the NMJ area Outside the NMJ, voltage gated Na-channels respond to this graded depolarization and open, triggering an Action potential along the sarcolemma 40 20

NeuroMuscular Junction Action potential (AP) Nucleus Myelinated axon of motor neuron Axon terminal of neuromuscular junction Sarcolemma of the muscle fiber 1 Action potential arrives at axon terminal of motor neuron. 2 Voltage-gated Ca 2+ channels open and Ca 2+ enters the axon terminal. 3 ACh relesed into synaptic cleft area Ca 2+ Ca 2+ Axon terminal of motor neuron Fusing synaptic vesicles Synaptic vesicle containing ACh Mitochondrion Synaptic cleft 41 NeuroMuscular Junction Axon terminal Synaptic cleft Open Na + Channel Na + Closed K + Channel ACh Na+ K+ ACh Na + K + + ++ + ++ 6 K + Action potential + ++ + ++ 4 5 ACh binds to and opens nicotinic Na-channel local depolarization: generation of the end plate graded potential on the sarcolemma Sarcoplasm of muscle 42 fiber 21

Sarcolemma Action Potential Depolarization due to Na+ entry Na + channels open Na + channels close, K + channels open Repolarization due to K + exit Threshold K + channels close 43 Excitation-Contraction (E-C) Coupling Excitation-Contraction coupling is the sequence of events by which transmission of an AP along the sarcolemma leads to sliding of the myofilaments There is an initial latent period: this is the time between AP initiation and the beginning of contraction Time when the molecular/cellular aspects of E-C coupling events occur 44 22

Steps in (E-C) Coupling Steps in E-C Coupling: Volt age-sensitive tubule protein 1 Action potential is propagated along the sarcolemma and down the T tubules. T tubule Sarcolemma Ca 2+ release channel Terminal cisterna of SR 2 Calcium ions are released. Ca 2+ 45 Steps in (E-C) Coupling Ca 2+ Troponin Actin Tropomyosin blocking active sites Myosin Active sites exposed and ready for myosin binding 3 Calcium binds to troponin and removes the blocking action of tropomyosin. Myosin cross bridge 4 Contraction begins 46 23

Muscle fiber Contraction Starts when calcium binds to troponin, allowing tropomyosin to shift out of the way and un-block the myosin head binding sites. ATP will now provide the energy so that the myosin heads pull back and forth on the actin strands, creating the sliding of thin over thick filaments The pulling of myosin heads on actin occurs via cross bridge formations The direction of the pull is towards the middle of each sarcomere Each mysoin head will cycle back and forth like a rower in a rowboat as long as calcium and ATP is available in the cytoplasm 47 Muscle fiber Contraction: Powerstroke The powerstoke occurs when the myosin head actually pulls on actin. Actin It occurs when the myosin head lets go of hydrolyzed ADP ATP ( ADP and Pi) Myosin cross bridge ADP Pi Thick filament 1 Cross bridge formation. The binding of an ATP molecule to the myosin head, the energizing of the myosin head by splitting ATP and the release of that energy via the powerstroke, are very similar to putting an arrow into a bow and putting tension on the bowstring. The powerstroke is then similar to letting the arrow fly. 2 ADP Pi The power (working) stroke. 48 24

Myosin head (high-ener gy configur ati o n) ADP Pi 1 Myosin head attaches to the actin myofilament, forming a cross bridge. Thin filam ent ATP hydr olysis ADP Pi Thick filam ent ADP 2 4 Inorganic phosphate (P i) gener ated in the As ATP is split into ADP and Pi, the m yosin previous contraction cycle is released, initiating head is energized (cocked into the high-energy the power (wor king) str oke. The m yosin head confor m atio n). pivots and bends as it pulls on the actin filament, sliding it toward the M line. Then ADP is released. ATP ATP Myosin head (low-ener gy configur ati o n) 3 As new ATP attaches to the myosin head, the link between myosin and actin weakens, and the cross bridge detaches. 49 Muscle fiber Contraction: Powerstroke The important aspect is that ATP needs to bind to the mysoin head in order for the mysoin head to detach from the actin The splitting of ATP into ADP and Pi provides the potential energy by snapping the head back into a potential powerstoke position. (like the pulling on the string of a bow to transfer the energy into the string as potential energy) During a single contraction, about 50% of the mysoin heads are puling while 50% are re-setting themselves A single sarcomere does not have to shorten much in order to get a muscle group to shorten 1 cm ( for ex: if a muscle cell has 10,000 sarcomeres one after another, how much does each need to shorten?) 50 25

End of a Single Contraction: Relaxation a single nerve impulse needs to correlated with a single muscle contraction released ACh in the synaptic cleft of the NMJ diffuses away AND is quickly destroyed by AcetylCholine-esterase. this prevents continued muscle stimulation in the absence of nerve impulses. 51 End of a Single Contraction: Relaxation In addition, strong Ca 2+ pumps operate at the SR level : from the moment Ca 2+ floods the cell, they start pumping it back into the SR Thus the cell only sees a brief increase in Ca 2+ : when calcium vanishes, the binding sites on actin become blocked again and the contraction stops! The SR also contains special proteins that bind Calcium strongly ( Calsequestrin) : This increases the holding capacity for Calcium in the SR and facilitates the reuptake of Calcium 52 26

Excitation-Contraction Problems Duchenne s Muscular dystrophy genetically inherited disease (only males affected) degenerative muscle weakness, paralysis and cardiac problems usually die before age 20 Related to lack of protein dystrophin Protein is suspected to play a role in calcium regulation and stability of sarcomeres Myastenia Gravis Results from progressive loss of ACh receptors Due to autoimmune response attacking the receptors Botulism Results from consumption of contaminated canned food progressive loss of ACh receptors Toxin prevents release of Ach (results in paralysis) 53 Excitation-Contraction Problems Curare binds to nicotinic receptors it thus blocks the ACh receptor: no muscle contraction Organophosphates : pesticides, nerve gas inhibit ACh-esterase maintained depolarization maintained contraction and no relaxation possible ( think what it will do to your diaphragm) 54 27

ATP versus Calcium Supply Of the two important molecules for muscular contraction, ATP and Calcium, which one would be the fastest in short supply? 55 Function of ATP 56 28

Rigor Mortis Following the death of an organism, cellular homeostasis and integrity breaks down No circulation, no oxygen supply to tissues No mitochondrial activities, no ATP production Calcium leaks into the cell and cannot be pumped out Binds to troponin ; tropomyosin shifts out of position Myosin binds to actin But there is no ATP for the power stroke or to release myosin from actin Muscles become locked in place at the thinthick filament level 57 29