Muscle Physiology
Generation of an Action Potential
1)An event causes the cell membrane of an excitable cell to depolarize to threshold 2)Responding to the change in voltage, voltage-gated NA+ channels to open allowing Na+ to flood into the cells causing a reversal of polarity - the region along the inner surface of the membrane is now 30mV more positive than the region along the outer surface. 3)The reversal of polarity causes the voltage-gated Na+ channels to close and voltage gated K+ channels to open; K+ flows out of the cell. 4) K+ outflow repolarizes the membrane (the loss of positive charges make the inner surface of the membrane more negative); repolarization triggers voltage-gated K+ channels to close; but K+ channels are slow and more K+ leaves than needed resulting in hyperpolarization 5) Na+/K+ exchange pumps pump out three Na+ for every two K+ pumped in, membrane returns to resting state.
stimulation of skeletal muscle
ACh diffuses across the synaptic cleft and binds to ACh receptors on sarcolemma, opening Na+ channels. Na+ rushes into muscle fiber, depolarizing the sarcolemma. The depolarization of the sarcolemma in response to a chemical signal from a motor neuron is the transmission of a command from the neuron to the muscle fiber to contract. The motor neuron, by means of an actional potential that caused the release of a chemical signal (Ach), has stimulated an action potential in the muscle fiber. Note that AChE is binding to any ACh that is left in the cleft and degrading it
How does Muscle Contraction Begin?
1.Motor neuron action potential reaches NMJ, releasing acetylcholine (ACh) 2.ACh binds to receptors on the sarcolemma openin ligand-gated Na+ channels open 3.Na+ enters and depolarizes the sarcolemma to threshold, starting an action potential in the muscle fiber 4.Action potential (electrical impulse) spreads over sarcolemma and down into the transverse tubules 5.T-tubules carry the actional potential over the terminal cisterns of the sarcoplasm reticulum 6.Sarcoplasmic reticulum (SR) releases Ca++ into the sarcoplasm where it binds to troponin 7.Binding of Ca++ to troponin causes a conformation change in troponin that pulls on the tropomyosin, exposing the myosin binding sites on actin 8.Myosin heads bind to the F actin filament 9.Myosin head lurches forward, pulling actin towards the center of the cell 10.The contraction cycle has begun
Refractory Periods
Absolute refractory period •The period of time after an action potential in which the sarcolemma cannot respond to any further stimulus regardless of the strength of the stimulus (number of action potential) •Occurs when voltage gated Na+ channels are already opened Relative refractory period •The period of time after an action potential in which the sarcolemma can respond only to very strong stimulus •Occurs when voltage gated Na+ channels are closed and voltage gated K+ channels are closing or about to close
Stimulation of Skeletal Muscle
Action potential of the neuron (in red) has swept down the axon and reaches the synaptic end bulb of the axonal terminal The effect of the neuron's action potential on the synaptic bulb is to cause exocytosis of synaptic vesicles, releasing ACh into the synaptic cleft
Aerobic Cellular Respiration
Aerobic cellular respiration starts with glycolysis in which a molecule of glucose is catabolized to two molecules of pyruvate (pyruvic acid) releasing energy to phosphorylate two molecules of ADP into ATP. Products of glycolysis: •two molecules ATP •two molecules of pyruvate. In the presence of oxygen, the pyruvate from glycolysis, is transferred to the mitochondria, the site of aerobic cellular respiration.
Cause of Rigor mortis
After death, cells lose the ability to maintain homeostasis. The control of ATP synthesis and all other metabolic reactions slowly ends over a period of a 3-4 hours. These reactions occur after death because molecules, including enzymes, have inherent energy and metabolic reactions are naturally occurring reactions. But all neural and hormonal homeostatic mechanisms and controls end. •Myosin in muscle fibers will automatically activate for as long as supplies of ATP last. •But all mechanisms that kept Ca++ in the sarcoplasmic reticulum no longer function. •Neural control over muscle contraction ends, no action potentials from motor neurons to stimulate prime movers, no targeted inhibition of antagonists •Ca++ leaks out of the SR allowing activated myosin heads to bind to actin and causing the simultaneous, uncontrolled contraction of all muscles, both prime movers and antagonists •In living cells, neurons stimulate the prime mover and decrease stimulation of antagonist so prime mover contract, antagonist relaxes •Contraction cycles in agonists and antagonists continue to cause maximal contraction •ATP runs out and the myosin heads cannot detach from the actin filament. The cross bridges do not break down. The actin filaments, held by their attachment to the myosin heads, cannot slide back and relax the muscle. •Contraction is maintained until proteolytic enzymes begin to decompose the proteins of the myofilaments ATP is needed for the both the activation of myosin and for the detachment of myosin from actin to allow muscle relaxation
Muscle Tissue
Alternating contractions (shortening) and relaxation of cells. Chemical energy changed into mechanical energy
Skeletal Muscle
Attaches to bone, skin or fascia Striated with light and dark bands visible with scope voluntary control of contraction and relaxation regulated by the primary motor cortex of the frontal lobe in the somatic nervous system
Action Potential
An action potential is the flow of electricity - it is an electric impulse carried by the flow of electrically charged particles in excitable cells such as neurons and muscle fibers. Neurons transmit signals, commands and information by means of action potentials that release chemicals known as neurotransmitters that initiate the intended effect of the action potential in an effector. The stimulation of a neuronal action potential on a muscle fiber causes an action potential in the muscle fiber. The transmission of the electrical impulse from neuron to muscle fiber transmits a command to the muscle fiber to contract. In muscles fibers: •Sarcolemma is polarized - positive charges, Na+, cluster on the outer surface of the sarcolemma, negative charges cluster on inner surface •Sarcolemma is nearly impermeable to Na+ (small amounts enter through leak channels) •Separation of electrical charges creates the resting membrane potential - potential electrical energy. •Sarcolemma has membrane proteins that form voltage-gated sodium ion channels, •When these gated channels are opened, Na+ floods into cell, depolarizing the sarcolemma and releasing stored potential electric energy •Electrically charged Na+ floods into cell, flows along the inner surface of the sarcolemma, causing an electrical impulse known as the muscle action potential •The muscle action potential converts stored electric energy into mechanical energy that moves the myosin head, attached to actin, pulling the thin filament in towards the center of the sarcomere; the thin and thin and thick filaments slide past each other shortening the sarcomere which shortens the muscle fiber
Contraction Cycle
As the actional potential sweeps across the sarcolemma and is carried deep into the sarcoplasm as it flows through T-tubules. The T-tubules bring the action potential across the surface of the terminal cisterns of the SR, causing the Ca++ channels to open and Ca++ to flow out the SR, into the sarcoplasm, where it will bind to the Ca++ binding sites on troponin. This results in a conformation change that exposed the myosin binding sites on actin.
Atrophy and Hypertrophy
Atrophy - wasting of muscles caused by •disuse (disuse atrophy) - reversible •loss of nervous stimulation (denervation atrophy) - irreversible • Hypertrophy - increase in the diameter of muscle fibers as a result of exercise or changes in daily activities
Sliding Filament Mechanism of Construction
Basic steps: 1.Myosin binding site on actin are unblocked 2.Myosin heads form cross bridges between thin and thick filaments by binding to actin 3.Movement at the hinge region of myosin acts to pull thin filament toward M line, 4.Thin filaments slide past the thick filaments and are pulled towards center of sarcomere, 5.Actin pulls Z discs at each end of the sarcomere, towards each other, 6.Shortening the sarcomere, 7.Shortening the muscle fiber 8.Contracting the muscle Note: the thick & thin filaments do not change in length - they slide past each other
skeletal muscle
Connective Tissue Components: •Superficial fascia - loose connective tissue underlying the skin •Deep fascia - dense irregular connective tissue around muscle •Connective tissue components of the muscle include -Epimysium: surrounds the whole muscle -Perimysium: surrounds bundles (fascicles) of 10-100 muscle cells -Endomysium: separates individual muscle cells, very thin layer of areolar tissue •All these connective tissue layers extend beyond the muscle belly to form the tendon that attaches the muscle to bone •Deep to the endomysium is the cell membrane of muscle cells •Multiple layers of connective tissue serve to allow individual components of skeletal muscle, from individual muscle fibers to the whole muscle, to function independently when necessary
Thick and Thin Myofilaments within a Myofibril
Dark(A) & light(I) bands visible with an electron microscope
Neuron Structure
Dendrites- processes that pick-up information (stimuli); neurons can have one or many dendrites, gathering information from multiple areas, relaying it to cell body Cell body (soma)- contains all organelles, nucleus, mitochondria, ribosomes, etc. Axon- relays information to an effector in response to stimuli; usually only one axon but the axonal terminal can divide into multiple end-points called synaptic bulbs. Synapse- the junction or interface between an axon terminal, or synaptic bulb, and the effector Synaptic cleft- narrow space separating the axonal terminal and the effector
Smooth Muscle Contraction: Features of Smooth Muscle
Dense bodies: -Protein structures similar to the proteins that form the Z line in sarcomeres -Attached to thin filaments and to the sarcolemma stabilizing the filaments and holding them in place -Connected to other intracellular dense bodies by intermediate filaments forming a network of contractile filaments within the cell -Extend out of the sarcolemma to form links to dense bodies in other smooth muscle cells to maintain the integrity of the smooth muscle as a functional tissue and to allow for communication between muscle cells for the coordination of contraction/relaxation cycles. Ca++ availability and regulatory proteins -Sarcoplasm reticulum: not extensive, cannot store much Ca++ but does store some. The sarcolemma has open Ca++ channels and Ca++ enters cells from extracellular fluid or blood to augment the amount of Ca++ that is released from the sarcoplasmic reticulum. -Calmodulin: because smooth muscle does not have troponin, cross bridge formation is not regulated by the troponin-tropomyosin complex. Calmodulin fills this role -Caveolae: pouch-like invaginations of the sarcolemma that take the place of transverse tubules. Smooth muscle fibers are much smaller and narrower than skeletal muscle fibers. A complex system of tubules to carry the actional potential deep into the fiber is not necessary because these fibers are so much smaller than skeletal muscle fibers
aerobic cellular respiration
Electron Transport Chain (ETC): •H+ concentration gradient puts a great deal of pressure on H+ to move with gradient • •At the end of each ETC is a H+ channel, this is the only place where H+ can move with their gradient; H+ rush through the channel and the rapid flow of H+ releases enough energy to produce ~ 30 molecules of ATP • •Also at the end of the ETC is oxygen - as H+ pass through the channel, two hydrogens are bound to an oxygen forming H2O
Aerobic Cellular Respiration
Electron transport chain: A chain of molecules embedded in the inner membrane, the cristae, of the mitochondria •Electrons are transferred from one component of the chain to another •Each transfer releases small amounts of energy that is used to pump H+, (from the critic acid cycle) into the inner compartment of the mitochondria creating a concentration gradient
Anaerobic Cellular Respiration - Glycolysis
Glycolysis - production of ATP from the catabolism of glucose in the absence of oxygen Process of Glycolysis •Begins with glucose from blood or muscle glycogen catabolism to release glucose •6-carbon glucose is broken down into two molecules of 3-carbon pyruvic acid •Energy released by glucose catabolism is used to produce two molecules of ATP If O2 levels are low: •pyruvic acid is converted to lactic acid which diffuses into the blood •lactic acid build up in muscle fibers during strenuous exercise causes muscle aches that resolve within days •Glycolysis can continue anaerobically to provide ATP muscle contractions for about a minute If O2 is sufficient - products of glycolysis are funneled into aerobic respiration
aerobic cellular respiration
In the mitochondria, 2 molecules of pyruvate go through two sets of reactions: - citric acid cycle •- electron transport chain Citric acid cycle (CAC): •C6H12O6 + 6O2 > 6CO2 + 6H2O (formula for the complete hydrolytic catabolism of glucose) •Complete catabolism of glucose produces 6 CO2, one for each of the 6 carbons in glucose and 6 molecules of water as well as two more molecules of ATP and lots of H+ •The H+ are transferred to the second set of reactions - the electron transport chain
Isotonic and Isometric Contractions
Iso = "same or constant"; Tonic = tension or strength; Metric = length •Isometric contractions: -Force increases but the length of muscles stays the same -There is no movement of body parts or limbs; but force is generated -Isometric exercises, a component of physical therapy and very useful when a global pandemic shuts down the gym, involve the static and intense contraction of muscles without discernible movement or change in the angle of a joint; for example - hands placed in front, palm to palm, at the level of the sternum and press the palms together as firmly and with the maximum amount of force personal capacity allows. Generation of significant force but muscles do not shorten or lengthen - •Isotonic contractions: -Same force or constant increase in force as length of muscle changes -Two types of isotonic contractions: •Isotonic concentric contractions •Isotonic eccentric contractions
Part of Twitch Contraction
Latent Period (blue vertical stripe) •10-20 msec •Neural action potential stimulates muscle •Ca++ released from SR, binds to troponin Contraction Period (green stripe) •10 to 100 msec •Filaments slide past each other •Motor units recruited as needed •More action potentials received as needed Relaxation Period (light yellow stripe) •10 to 100 msec •Active transport of Ca++ back into SR •Gated K+ channels open •Membrane repolarizing to resting state Refractory Period (dark yellow stripe) - • Muscle fiber is hyperpolarized •5 msec for skeletal; 300 msec for cardiac muscle •Slow closing of gated K+ channels •Muscle can not respond to normal stimuli; •Can respond to greater stimuli •Absolute and relative refractory
Types of Smooth Muscle
Multi-unit Smooth Muscle •Found in limited number of body areas: large blood vessels, respiratory airways, iris of the eye •Innervated by neurons of the autonomic nervous system (ANS) in motor units that appear similar to those in skeletal muscle but are not; a skeletal muscle fiber in a motor unit is only innervated by an axonal branch of one motor neuron making the fiber a member of a unit of muscle fibers innervated by that one motor neuron; multi-unit smooth muscle fibers are innervated by axonal branches of more than one motor neuron; not a unit Visceral Smooth Muscle •Not in contact with a motor neuron •Form sheets or layers of smooth muscle fibers, closely linked together by dense bodies and electrically connected to one another by gap junctions through which an actional potential can flow from cell to cell, causing a contraction that sweeps across the entire layer of fibers •Contractions can be initiated by an ANS neuron, hormones, local factors such as stretching, concentrations of metabolic products, etc. •Pacemaker cells - autorhythmic cells capable of spontaneously generating an action potential at regular intervals usually through a very precise number of carefully placed open Na+ channels that allow Na+ to enter the cell at a steady rate that is sure to result in the depolarization of the sarcolemma that initiates an action potential. The rate at which Na+ can enter the cells establishes the timing of the action potential which will be spread throughout the layer of cells. Pacemaker cells establish the pace at which contractions will occur without regulation or control of neurotransmitters, hormones or local factors
Muscle Fatigue
Muscle fatigue - the inability of muscles to accomplish a level of activity. Common factors are: -Drop in pH of the muscles from relying on glycolysis - Glycolysis is useful because it is the quickest way to generate ATP, but it is not efficient (produces only 2 molecules of ATP for one molecule of glucose) and the products of glycolysis include lactic acid which can lower pH of blood, other fluids and tissues. -Decreasing levels of Ca++ - we store good quantities of Ca++ in the sarcoplasmic reticulum but it is not a bottomless pit. Muscle contractions are not the only important activity that requires Ca++ and depletion can occur -Decrease in Ca++ binding to troponin, lower levels of Ca++ result in less Ca++ to bind to troponin Lactic acid - -Most is produced during the peak of activity -Diffuses out of muscles, into blood, and to the liver -Liver recycles lactic acid -When activity is over, lactic acid in muscles can be converted into pyruvate, enter the citric acid cycle and electron transport system to generate ATP and build up supply - Recovery - -Paying the oxygen debt -Oxygen debt is the amount of oxygen you need to restore body conditions to resting state; this includes building up stores of ATP, creatine phosphate, and myoglobin -Respiratory rate will remain elevated until debt is paid
Muscle actions in body movement
Muscles work in pairs: an agonist, the prime mover, that accomplishes the action, and an antagonist, that opposes the action. Both the agonist and the antagonist pull on the same bone or bones. To create movement, one to has to contract and the other has to relax. The opposing muscle must relax to allow the prime mover to carry out the action. •If both muscles contract, the limb or body part cannot move. •To lift a book from your desk, the prime mover is the biceps brachii muscle of the anterior forearm. The biceps contracts and the shortening of the muscle pulls on the bones of the forearm, flexing the forearm and lifting the book. But the antagonist must allow this movement by relaxing. •The antagonist, the triceps brachii on the posterior forearm, relaxes so the biceps can contract and lift the book •No method of stimulating or signaling muscles to relax, muscles relax with decreased stimulation •All muscles are always slightly contracted; they constantly receive minimal stimulations that cause mild involuntary contraction of scattered muscle fibers throughout the muscle to maintain muscle tone and keep muscle firm, even in sleep or coma •To cause movement, motor neurons stimulate prime movers to contract with multiple action potentials, while decreasing the minimal stimulations to the antagonist muscle, inhibiting the muscle, decreasing the minimal contraction that maintains muscle tone, causing the antagonist to lengthen and allow the movement to occur •In rigor mortis every muscle in the body, agonists and antagonists, is contracted making the body, from head to toe, as stiff as a plank of wood.
Myofibrils and Myofilaments
Myofibril - •cylindrical structures that run the length of a muscle fiber; •there can be hundreds or thousands of myofibrils in a single muscle fiber, (muscle fibers are large cells); •each myofibril is surrounded by the sarcoplasmic reticulum which separates myofibrils; •myofibrils contains myofilaments Myofilaments - •thread-like protein filaments; contractile proteins •function to contract and relax the muscle fiber •thin filaments composed mostly of actin •thick filaments composed mostly of myosin •myofilaments are organized into sarcomeres
Neuromuscular Junction (NMJ) a Synapse
NMJ = neuromuscular junction - a synapse between a neuron and a muscle fiber -end of axon (synaptic bulb) near muscle fiber at a region of the sarcolemma called the motor end plate; motor end plate of the muscle fiber and synaptic bulb of the neuron are separated by the synaptic cleft -Synapse: the interface at which a neuron can transmit a chemical signal or command that initiates a specific response by the cell or structure receiving the signal or command
Smooth Muscle Contraction
Neural Control of Smooth Muscle Contraction Neural control by the autonomic nervous system (ANS) -Axons of ANS neurons have bulges or varicosities along their length in which neurotransmitters accumulate. These axons weave loosely through muscle cells and an action potential flowing along the axon will trigger release of the neurotransmitter. An ANS neuron can release either acetylcholine or norepinephrine from viscosities; one will be stimulatory and the other inhibitory but there is no rule as to which does what where. Neural Control of Skeletal Muscle Contraction Skeletal muscle cannot be inhibited or stimulated to relax. It can only be stimulated to contract by acetylcholine and every muscle fiber in a muscle must be individually innervated. But smooth muscle fibers are much smaller and dense bodies link smooth muscle fibers closely together so that an impulses to either contract or relax spread from one fiber to another Hormonal Control of Smooth Muscle Contraction Many circulating hormones influence smooth muscle contraction because smooth muscle forms the walls of many organs. Hormones that regulate the function of those organs must have an effect on the smooth muscle. For instance, the walls of major arteries are lined with smooth muscle. Contraction of smooth muscle helps to pump the blood through the body. Blood pressure must be maintained, or blood cannot be pumped. Blood pressure is the pressure that blood exerts on the walls of arteries and veins. Hormones that function to regulate blood pressure, such as angiotensin that raises blood pressure, have multiple effects but one of its effect is to stimulate smooth muscle to contract. Contraction of the smooth muscle in artery walls will decrease the diameter, the size, of arteries. If the same amount of blood is in two arteries, one artery is small and the other large, blood pressure will be higher in the smaller artery. Skeletal muscle does not respond to hormones. Local Factor Control of Smooth Muscle Contraction Smooth muscle contraction can be stimulated or inhibited by local factors. For instance, stretching of the intestinal walls can stimulate a contraction of the smooth muscle that forms the walls of the intestinal tract. Skeletal muscle contraction is rarely affected by local factors
Microscopic Anatomy of Smooth Muscle
No sarcomeres, no striations Myofilaments Thin filaments with actin as a significant component, are attached to and anchored by dense bodies, proteins very much like those that form the Z line in skeletal muscle sarcomeres. Dense bodies are fastened to the sarcolemma and to thin filaments Thick filaments are found throughout the sarcoplasm of smooth muscle cells, near dense bodies and thin filaments, in a ratio of ten thin filaments to every one thick filament which is very different from the ratio of 2:1 seen in cardiac and skeletal muscle Intermediate filaments form a network that connect dense bodies in the sarcoplasm. Dense bodies, in addition to the functions mentioned above, also serve to facilitate communication among smooth muscle cells and to link cells together. Dense bodies are fastened to the sarcolemma and connected to other dense bodies in the cell by intermediate filaments. This forms a network od dense bodies - an important feature in smooth muscle contraction. In addition, dense bodies from neighboring cells link neighboring cells together so the impulse to contract will pass from one cell to another and coordinate contractions.
Proteins of the Myofibrils - Thin Filament
Note: •G-actin forming filamentous F-actin •Active site - myosin binding site, on G actin •Double stranded tropomyosin blocking the myosin binding sites •The three subunits of troponin: •One binds to tropomyosin forming troponin-tropomyosin complex •One binds to actin - holding the troponin-tropomyosin complex in place, blocking the myosin binding sites •One has a binding site for two Ca++
Contraction of Smooth Muscle
Note: •Thin filaments (in red) attached to dense bodies •Thick filaments (in grey) •Dense bodies anchoring thin filaments •The network formed by intermediate filaments attached to dense bodies •The single nucleus in a fusiform shaped smooth muscle •In top diagram - a relaxed smooth muscle fiber •In middle diagram - two relaxed smooth cells linked to one another by dense bodies to allow an action potential to flow from one cell to another •In the bottom diagram - a contracted smooth muscle fiber; note how the intermediate filaments have essentially pulled the cell into it contracted state as thin and thick filaments slid past each other
Functions of Muscle Tissue
Producing body movements Stabilizing body positions Regulating organ volumes Movement of substances within the body Producing heat
Contraction Cycle
Sequence of events causing the thick and thin filaments to slide over each in other bring about contraction is as follows: •ATP hydrolysis activates myosin whenever ATP is available; myosin is always activated in living cells so it can respond immediately •Sarcolemma is depolarized - an action potential in muscle fiber - release of Ca++ from SR •Ca++ binds to troponin; troponin changes shape, pulls tropomyosin off binding sites •Attachment of myosin to actin forms cross bridges between filaments •Power stroke - movement at the hinge region of myosin yanks the actin filament towards the center of the sarcomere shortening the sarcomere, shortening the muscle fiber and the muscle contracts •If ATP is present, myosin detaches from actin, dephosphorylates another molecule of ATP and is reactivated •Reactivated myosin head attaches to another section of the thin filament and yanks the filament further in towards the center of the sarcomere further decreasing the length of the sarcomere and increasing the contraction •Cycle of myosin binding to actin, pushing the filament inward, detaching and reactivating, keeps repeating as long as ATP and Ca++ are available
connective tissue component of skeletal muscle
Skeletal muscle cells are called muscle fibers. They have a unique cellular structure in which cellular features are highly modified to accomplish special tasks. Sarcolemma - cell membrane of muscle fibers, located just deep to endomysium Sarcoplasm - cytoplasm of muscle fibers Sarcoplasmic reticulum - endoplasmic reticulum of muscle fibers.
Nerve and blood supply
Skeletal muscle highly innervated and well-vascularized. •Skeletal muscle contracts when stimulated via neuronal pathways that originate in the frontal lobe of the brain - the primary motor cortex; •Motor neurons, exit the central nervous system (brain and spinal cord), and extend to innervate individual muscle fibers. One motor neuron will innervate multiple muscle fibers scattered throughout a muscle. •The part of the neuron involved in the innervation of a muscle fiber is the axonal terminal or synaptic bulb •The part of a muscle fiber involved in innervation is the motor end plate •The interface between the motor neuron and the muscle fiber is known as the neuromuscular junction (NMJ) •The nervous system can only stimulate muscle to contract; muscles relax when stimulation is decreased; no signal or command to relax •The neural fibers of motor neurons and blood capillaries are found in the endomysium between individual muscle fibers
Microscopic Anatomy of Smooth Muscle
Smooth muscle is sometimes referred to as visceral muscle because it forms the walls of visceral organs such as the gastrointestinal tract. It is not used very often because smooth muscle is found in many other organs in addition to viscera such as the arrector pili muscle or the iris of the eye. •Small, involuntary muscle cells, fusiform with tapered ends •Single, oval, centrally located nucleus •Cells: -Lack transverse tubules -Have very little sarcoplasm reticulum for Ca+2 storage -Do not have troponin, calmodulin performs similar functions
Complete (Fused) and Incomplete (Unfused) Tetanus
Tetanus is prolonged muscle contraction caused by rapidly repeating stimuli. The serious bacterial infection caused by Clostridium tetani is called tetanus because symptoms are a severe, unrelenting, spastic contraction of muscles. Lockjaw •Unfused tetanus -stimulation at 20-30 times/second - only partial relaxation between stimuli • Fused tetanus -stimulation at 80-100 times/second - sustained max contraction
Isotonic Eccentric Contractions
The force generated is less than the load, muscle lengthens Muscles tend to work in pairs •Most movements involve a prime mover or agonist, the muscle directly responsible for the action; and an antagonist, the muscle that allows the action to occur. •In biceps curls, the biceps brachii is the prime mover. It must generate force greater than the load in order to lift the load. The biceps brachii has an isotonic concentric contraction as seen in last slide. •BUT - the biceps brachii cannot be flexed unless the antagonist muscle extends and allows for the flexion of the biceps •The triceps brachii is the antagonist muscle in biceps curls •It generates a force that is less than the load, meaning that it is less than the force needed to lift or move the load •The triceps lengthens (extension) allowing the biceps to flex
Isotonic Concentric and Eccentric Contractions
The muscle exerts a force greater than the load; it shortens and moves the load. The force stay the same - isotonic. The muscle exerts a force less than the load, the muscle maintains the same level of force (isotonic), but it lengthens to allow extension of the agonist and/or because of the pull of gravity.
Transverse Tubules
The sarcolemma of muscle fibers does not just wrap around the outer surface of the cell. It invaginated deep into the muscle fiber forming tubules that transverse the sarcoplasm - transverse tubules. (Often called T-tubules) These tubules are filled with extracellular fluid and their function is to carry the impulse for muscle contraction deep into the muscle fiber. Sarcoplasmic reticulum - wraps around myofibrils and functions to store calcium ions; the membrane that forms the reticulum contains membrane proteins that act as Ca++ pumps, that pump Ca++ into the reticulum keeping intracellular levels of Ca++ low. At the site of the transverse tubule invaginations, the reticulum forms enlarged spaces called terminal cisterns. A transverse tubule runs over these enlargements forming a triad; (triad = three) triads consist of two terminal cisterns of the endoplasmic reticulum and a transverse tubule
Myosin Activation
Whenever ATP is available, myosin heads will activate and stay activated until the contraction cycle begins. In living cells, myosin is always activated and ready to respond to an action potential. •Note in the diagram that ATP has already been dephosphorylated - a high energy phosphate bond has been hydrolyzed from ATP (adenosine triphosphate) to form ADP (adenosine diphosphate phosphate) and phosphate (P or Pi or iP - P for phosphate and i for inorganic). • •The chemical energy from ATP hydrolysis is stored in the tilted head of myosin as illustrated by the presence of ADP and P on the tilted myosin head in the diagram (think of pin ball- when you pull on the knob of a pin ball machine, you "activate" the spring on the other side of the glass. You impart energy to the spring that is part of knob apparatus. As long as you hold onto the knob, it is potential energy, energy that is stored in the tight coils of the spring. When you let the knob go, the energy in the spring is released, the spring shoots forth to hit the pinballs.) • •The activation of myosin tilts the myosin head backwards, so it is at about a 1100 angle to the myosin tail • •Though myosin is activated, until an action potential causes the release of Ca++ from the sarcoplasm reticulum, nothing happens; the myosin head stays in the activated position • •Note that Ca++ has not bound to troponin and that tropomyosin is still blocking myosin binding mites on actin
contraction cycle
With myosin binding sites on actin exposed, the myosin heads bind to actin.
Ligand
a molecule that binds to another, specific molecule by virtue of complimentary 3-D structures. Ligand gated channels are usually membrane proteins channels that can be opened or closed when a specific ligand bonds to a complimentary site on the protein channel. Remember that a protein's function is related to and dependent on, its structure.
smooth muscle
in walls of hollow organs - blood vessels and gastrointestinal track nonstriated in appearance involuntary - regulated by autonomic nervous system
Structure of Mitochondria
note the inner membrane, the cristae, that creates an inner compartment called the matrix. The enzymes and the components of the electron transport chain are embedded in the cristae. Energy released during electron transport along the chain is used to pump H+ into the matrix creating a concentration gradient. Enzymes include ATP synthase to phosphorylate ADP
Refractory period
repolarization is due to K+ leaving the cell through gated channels. Gated K+ channels are slow. Slow to open and slow to close. As the membrane potential approaches resting potential, K+ channels start to close but they are too slow. This allows more K+ to leave the cell than is needed to restore membrane potential. Membrane is hyperpolarized - more negative than the resting membrane potential. For fiber to respond, stimuli must be strong enough to overcome hyperpolarization.
cardiac muscle
striated in appearance involuntary control autorhythmic - clusters of cells (nodes) rhythmically generate stimulus to contract
The Motor Unit
•A motor unit consists of one motor neuron and all the skeletal muscle fibers it innervates •Each motor neuron innervates muscle fibers that are scattered and dispersed throughout the muscle, so the contraction is also dispersed throughout muscle and not cramped in one area •Total strength of a contraction is affected by how many motor units are activated and how large the motor units are
Wave Summation and Strength of Contraction
•A subsequent stimulation after the refractory period but before complete muscle relaxation will result in a second contraction that is stronger than first [see (a) and (b)]. This is due to residual Ca++, fibers already partially contracted, voltage gated K+ channels still open adding to depolarization.
Role of ATP in muscle contraction
•ATP is needed to activate myosin and to allow it to detach and reactivate to perpetuate the contraction cycle •Role of ATP is two-fold : -activate myosin so the head is in a position to push the actin filament in towards M line -detach myosin head from actin allowing the myosin head to return to its inactive state and reactivate. •In the absence of ATP, myosin heads stay attach to actin filament • •The dual role of ATP in muscle contraction is clearly demonstrated in rigor mortis •Rigor mortis - muscular rigidity of all body muscles that begins 3-4 hours after death, lasts about 24 hrs •To understand rigor mortis, need to understand how muscles function to cause movement
Relaxation of Skeletal Muscle
•Acetylcholinesterase (AChE) (enzyme that breaks down ACh) is always present in the synaptic cleft •As soon as ACh is released from synaptic bulbs, AChE starts to break it down. •To increase or maintain contraction, the neuron must repeatedly stimulate the muscle with sequential actional potentials that release more ACh; this gives greater control over the duration of contraction and the contraction-relaxation cycles of different muscles (think how rapidly all the muscles of your hands have to relax and contract to varying degrees in order to type on a keyboard) •When neuronal action potential ends; AChE breaks down remaining ACh in the synaptic cleft •Without ACh: -sodium ion channels close, -sarcolemma repolarizes -muscle action potentials cease -Ca++ channels of sarcoplasmic reticulum close -Ca++ pumps on the membrane of the sarcoplasm reticulum rapidly pump Ca++ into the reticulum -Ca++ level in the sarcoplasm fall, no Ca++ left to bind to troponin -Troponin reverts to its original shape -Tropomyosin covers binding sites on actin, blocking myosin attachment -Myofilaments slide past each other, returning to their original position -Sarcomeres lengthen, muscle fibers length and muscle relaxes The trigger for muscles to relax and lengthen is the absence or decrease of Ach. There is no separate signal or mechanism for muscles to relax and lengthen.
Actin
•Actin is a globular protein - G actin -it has a spherical structure (G for globular) •Individual molecules of G actin link together to form a strand of G actin molecules •Two strands twist around one another to form the core of the thin filament - F actin (F for filament) •Every G actin molecule has an active site to which myosin can bind - a myosin binding site •In a relaxed muscle, the myosin binding sites on the actin filament are covered by tropomyosin
Strength of Contraction: Force Generated
•Action potentials are "all or none" •Demands on muscles are highly variable - from picking up a sheet of paper to bench pressing your body weight •Requires generating a wide range of force for daily activities •Strength of contractions determines the amount of force generated •Strength of contractions determined by: -Number of motor units recruited; •more motor units, greater force -Number of action potentials received by the muscle •more action potentials, greater force
Strength of Contraction: Frequency of Stimulation (action potentials)
•Action potentials are "all or none" •There are no weak or strong action potentials •It either happens or it does not happen at all •Frequency with which neural action potentials stimulate a muscle, determines the strength of the contraction •Summation, complete and incomplete tetanus •The greater number of actional potentials per milliseconds, the stronger the contraction •Stronger contractions = greater force generated •Greater force generated = more weight can be lifted, etc.
Excitable Cells
•All human cells are electrically polarized due to the unequal distribution of electrically charged particles on either side of the selectivity permeable cell membrane. •Both the extracellular and intracellular fluids are electrically neutral as a whole; but measuring the voltage across the cell membrane of a resting cell, reveals that the region of the cell closest to the inner surface of the membrane is approximately 70 mV more negative than that of the outer surface. •This electrical difference represents potential energy and is known as the resting membrane potential. •Most cells will experience disturbances of the membrane potential, but there are mechanism to quickly re-establish the polarization of the membrane •Excitable cells have a threshold that distinguishes between minor and significant disturbances of the membrane potential •Significant disturbances of the membrane potential of excitable results in the generation of an action potential •An action potential is an electric impulse that flows over the cell membrane of excitable cells •Neurons and muscle fibers are excitable cells in the human body
Stimulation of Skeletal Muscle
•An action potential flows down the axon of a motor neuron to the synaptic end bulbs. •Synaptic bulbs interface with motor end plate of a muscle fiber at the NMJ •Note the following features in this diagram: •Sarcoplasmic reticulum •Axonal terminal •Synaptic cleft •Motor end plate
Physiology of Smooth Muscle Contraction
•Contraction is stimulated an ANS neuron, a hormone or a local factor •Stimulus spreads over the sarcolemma and caveolae carry it into the sarcoplasm •External Ca++ enters the fiber thought through open Ca++ channels in the sarcolemma and additional Ca++ is released from the sarcoplasmic reticulum •Ca++ binds to calmodulin forming a Ca++- Calmodulin complex •Ca++-calmodulin complex activates a myosin light chain kinase, an enzyme that phosphorylates the myosin heads of thick filaments by dephosphorylating ATP •With the myosin heads now activated (and no tropomyosin to block myosin binding sites on actin), the myosin heads bind to actin filaments, pull on them and the thin and thick filaments slide past each other •The thin actin filaments are attached to dense bodies that are tethered to the sarcolemma and are connected to other dense bodies by intermediate filaments that form a network that permeates the sarcoplasm. •As the thin and thick filaments slide past each other, the thin filament pulls on the network of intermediate filaments and dense bodies, resulting tin he contraction of the smooth muscle fiber
Aerobic Cellular Respiration
•Essential for the production of enough ATP for any activity lasting over ~60 seconds -One creatine phosphate yields one ATP -One glucose in glycolysis yields two ATP -One glucose in aerobic respiration yields ~32 ATP
Creatine Phosphate
•Excess ATP in resting muscle is used to form creatine phosphate - a phosphate is transferred from ATP to creatine to forming creatine phosphate (CP) •When ATP is required, the phosphate is removed from CP and attached to ADP to form ATP •Cycling of a phosphate between ADP and creatine •Producing ATP by the transfer of a phosphate from creatine to ADP to produce ATP is known as substrate-level phosphorylation - the direct transfer of a phosphate group from a substrate (creatine phosphate) to ADP. •Creatine phosphate can not sustain muscle contraction for long Creatine dietary supplements - creatine is toxic, water soluble, associated with several diseases and must be kept within homeostatic parameters in the body or it will damage cells. The body will only retain a specific amount of creatine. Take in more than the body needs, and, like other water-soluble supplements, the body just dumps it into the urine. Stresses and overworks the kidneys. •Upon first starting creatine supplements, there is a temporary gain in muscle mass and performance but within a very short time, the body shuts down natural endogenous creatine synthesis and speeds up its elimination in the urine. •Overall, there is no real gain in muscle mass or performance
Properties of muscle tissue
•Excitability -respond to chemicals released from nerve cells •Conductivity -ability to propagate electrical signals across cell membrane (sarcolemma) •Contractility -ability to shorten and generate force •Extensibility -ability to be stretched without damaging the tissue •Elasticity -ability to return to original shape after being stretched
isotonic concentric contractions
•Force of contraction exceeds the load and so the load moves, and muscle shortens •Biceps curls in which you hold a dumbbell in your hand and flex the elbow to lift the weight of the dumbbell (which includes defying gravity; weight is a function of gravity) •Biceps generate a force greater than the weight of the dumbbell •Weight of the dumbbell does not change so the force of the contraction does not change - isotonic •Force rises at a constant rate as you lift the same amount of weight a greater distance •Note in the diagram that the weight remains at 2 kg, but the muscle shortens generating a force capable of lifting the 2 kg weight
Variations in Skeletal Muscle Fibers
•Human skeletal muscle has three major types of skeletal muscle fibers: -Fast, slow and intermediate fibers. •Within those categories, fibers are also classified as being red, white or pink. •Fast fibers are the most abundant in human skeletal muscle because they are fast and have a very short recovery period. But muscles will have fibers of all three types and will recruit them as needed for different tasks and activities •All fibers belonging to the same motor unit are the same type •The different types of fibers differ primarily in the quantity of myoglobin, mitochondria and capillaries found in the fibers. -Red muscle fibers: more myoglobin, more capillaries and mitochondria -White muscle fibers: less myoglobin, fewer capillaries •Differing quantities of mitochondria affect the method by which ATP is most often generated by the fiber - many mitochondria = aerobic respiration •Quantities of myoglobin reflect resistance to fatigue; myoglobin will provide access to oxygen beyond that delivered to fibers by the bloodstream, but high myoglobin also reflects a low use of glycolysis for ATP synthesis; aerobic respiration is slow and while it is more efficient and healthier, we also need speed
Role of ATP in muscle contraction
•If ATP is available, the newly inactivated myosin heads will bind to another molecule of ATP and the hydrolysis of ATP will reactivate the myosin head •If motor neurons continue to release ACh at the NMJ to maintain the action potential in the muscle fiber, Ca++ levels in the sarcoplasm remain high and the myosin binding site remain exposed •Activated myosin will again bind to its binding sites and pull the actin filament further towards the center of the sarcomere, continuing the cycle
stimulation of skeletal muscle
•In blue, is the axonal terminal with vesicles containing Ach (in red) •Note the synaptic cleft containing acetylcholinesterase (AChE), the enzyme that degrades Ach •As soon as ACh is released from the axonal terminal, AChE starts to degrade it; important control mechanism - allows the brain to precisely control the amount of ACh available at the NJM which in turn, controls the strength and intensity of the muscle contraction •Note the motor end plate of the muscle fiber with ACh receptors (in purple), ACh receptors are ligand-gated Na+ sodium channels
Anaerobic Cellular Respiration - Glycolysis
•In substrate level phosphorylation we produce one molecule of ATP from one molecule of creatine phosphate. •In glycolysis we produce two molecules of ATP from one molecule of glucose that is catabolized. •Neither of the above can generate enough ATP to meet the energy needs of the human body. •Together, they give us enough ATP to fuel muscle activity for a minute or two, sometimes less
Isotonic and Isometric Contraction
•Isotonic contractions = a load is moved -concentric contraction: a muscle shortens to produce force and movement - lifting a weight -eccentric contractions: a muscle lengthens while maintaining force and movement - lowering a weight •Isometric contraction = no movement occurs -tension is generated without muscle shortening -maintaining posture and supports objects in a fixed position
Motor Units
•Motor units in a muscle fire asynchronously, not all at same time -fibers belonging to any one motor unit are scattered throughout the muscle -at any point, some motor units are active others are relaxed -delays muscle fatigue so contraction can be sustained •Alternating stimulation of different motor units produces smooth muscular contraction -not a series of jerky movements because contractions are spread throughout muscle, not restricted to a few muscle fibers in one area, so even though only a portion of fibers are contracted at any given point, the effect is spread through the entire muscle •Precise movements require smaller contractions -motor units must be smaller (less fibers per motor neuron) -precision vs force; usually can't have both (arms and hands allow for more precise movements than legs and feet, but legs and feet can exert greater force) •Large motor units stimulate more muscle fibers than smaller units -large units are active or present when and where greater force is needed -smaller units allow for greater control and precision
Muscle Fiber
•Muscle fibers are long, cylindrical and multinucleated •Sarcoplasm is filled with myofibrils, numerous mitochondria, glycogen, and myoglobin •Glycogen - "animal starch"; a polysaccharide consisting of long chains of glucose monomers •Myoglobin - O2 binding protein, similar to hemoglobin Skeletal muscle must be able to react quickly. It must have a steady, unfaltering supply of glucose and oxygen to fuel muscle movements that can be vital to maintaining life. Other body cells depend on the bloodstream to deliver glucose and oxygen. Liver cells can store about 24 hours worth of glucose as glycogen. Liver glycogen is broken down to glucose and released into the bloodstream when blood glucose levels fall. Muscle fibers are the only cells that keep their own supply of glycogen for their own use. Muscle fibers are also the only cells that can store oxygen in myoglobin. When rapid muscle activity is required, muscle fibers can break glycogen down to glucose and take oxygen from myoglobin to produce ATP by aerobic respiration
Muscle Metabolism: Production of ATP in Muscle Fibers
•Muscle uses ATP at a great rate •Normal levels of sarcoplasmic ATP do not last long •ATP must be constantly produced to meet demand •Three sources of ATP production in muscle: •creatine phosphate •anaerobic cellular respiration •aerobic cellular respiration Cellular respiration - a set of metabolic reactions that convert biochemical energy from nutrients into stored energy in high energy phosphate bonds in adenosine triphosphate
The Proteins of Myofibrils
•Myofibrils contain three types of protein -contractile proteins •myosin and actin -regulatory proteins which control contraction •troponin and tropomyosin -structural proteins which anchor filaments, provide proper alignment as well as elasticity and extensibility •titin, myomesin, nebulin and dystrophin
Myofilaments in the Sarcomere
•Myofilaments in each myofibril are arranged in ~10,000 repeating units lined up end to end, called sarcomeres •Arrangement of myofilaments in sarcomeres cause the striated appearance of skeletal and cardiac muscle •I (isotropic) bands: iso = same; isotropic bands at rest contain primarily thin myofilaments •A (anisotropic) bands: an iso = not the same) anisotropic bands have thin and thick filaments •Thick and thin myofilaments overlap each other in a pattern that creates a pattern of alternating light and dark bands in each sarcomere •Sarcomeres are separated by Z lines (line looks like the letter Z) -The M line connects the central portion of each thick filament. -In the overlap region, six thin filaments surround each thick filament
Resting Membrane Potential
•Na+ and Cl- are the most abundant ions in the extracellular fluid •K+ is the most abundant positively charged ion in the cytosol of the cytoplasm. The positive charges of K+ are balanced by negatively charged proteins in the cytoplasm. •The membrane has both Na+ and K+ leak channels but number of K+ leak channels far outnumber Na+ •Na+/K+ exchange pump pumps two K+ into the cells while pumping three Na+ out • •Excitable cells have voltage-gated K+ and Na+ channels •Voltage-gated channels respond to changes in voltage •Voltage-gated Na+ channels respond quickly; voltage-gated K+ channels respond slowly
Clinical Conditions Affecting Skeletal Muscle
•Polio - virus attacks motor neurons in the spinal cord causing muscle atrophy and paralysis. One of the most feared diseases of the first half of the 1900's primarily because it attacked young children and young adults. Polio was eradicated in the United Stated after a massive national vaccination program was implemented. The country has not had a case since 1979 but wide-scale vaccination must continue because it is still present in other countries. •Myasthenia gravis - an autoimmune disorder in which acetylcholine receptors on the motor end plate of the neuromuscular junction are destroyed by the body's own immune system resulting in progressive weakness. •Muscular dystrophy - genetic disorder that causes progressive muscle weakness and deterioration usually leading to death by paralysis of respiratory muscles. It is caused by genetic mutations in the gene coding for the protein dystrophin. Dystrophin functions to stabilize and protect muscle fibers from damage by connecting the cytoskeleton of muscle fibers to extracellular support structures thus preventing damage to the muscle fibers and contractile proteins and keeping them intact. Inheritance is sex-linked, appearing more often in males.
Regeneration of Muscle
•Skeletal muscle fibers cannot divide after first year of life -growth of muscles is due to enlargement of existing cells -Repair: •limited regeneration by satellite cells •in extensive damage, replacement fibrosis (scarring) occurs •Cardiac muscle fibers cannot regenerate -all healing is done by replacement fibrosis •Smooth muscle fibers can regenerate -cells can grow larger (hypertrophy) -some cells (uterus) can divide (hyperplasia)
Muscle Tone
•Skeletal muscle is said to be "voluntary" but many aspect of skeletal muscle functions are not under conscious control (ie: shivering, muscle tone) •Muscle tone is due to the involuntary contraction of a small number of motor units scattered throughout all skeletal muscle, that alternately contracted and relaxed in a constantly shifting pattern -keeps muscles firm even though relaxed and not generating force -does not produce movement •Essential for maintaining posture (ie: holding your head upright and other aspects of skeletal muscle functioning that we are seldom aware of) •Smooth muscle also has muscle tone - important in maintaining blood pressure -tone of smooth muscles in walls of blood vessels •Degree of tone is largely genetic but can be improved with exercise -well toned muscles have a high metabolic rate, need more energy so they use up more calories -weight training (not body building) builds muscle tone and helps maintain weight as well as increasing the size of muscles
Transmission of an Impulse
•Stimulation of a muscle fiber involves the transmission of an electric impulse from a neuron to a muscle fiber. •The neurotransmitter acetylcholine, is a chemical signal that stimulates muscle fibers and initiates an action potential in the muscle fiber. •The effect of the actional potential in the muscle fiber will be to cause the fiber to contract. As the action potential spreads across the sarcolemma of the muscle fiber, it will be carried deep into the sarcoplasm by the transverse tubules. T-tubules run over the terminal cisterns of the sarcoplasmic reticulum. The action potential sweeping over the cisterns, causes the release of Ca++ into the sarcoplasm.
Muscle fibers
•Superficial to the sarcolemma of muscle fibers, are several layers of connective tissue that isolate individual fibers, fascicles, and muscles •Muscle fibers are covered by the endomysium •A bundle of muscle fibers form a muscle fascicle -Fascicles are encased by perimysium •Bundles of fascicles form a muscle -Muscles are encased by epimysium •Mature muscle fibers are large, multinucleated cells • •Mature muscle fibers can not divide, they are postmitotic; they can repair damage due to daily wear and tear, but severe damage requires assistance of satellite cells •Muscle growth is a result of cellular enlargement (hypertrophy) - not cell division (hyperplasia) •Satellite cells are stem cells that retain the ability to divide; after mitosis, one daughter cells remains a satellite cell (to maintain the population of satellite cells) and the other differentiates into a cell the functions to repair and regenerate muscle tissue
Thick and Thin Myofilaments
•Supporting proteins form the M line that anchors thick filaments, and the Z line that along with titan, anchors thin filaments. These proteins stabilize the sarcomere as they anchor the filaments in place.
Strength of Contraction: Motor Unit Recruitment
•Synaptic bulbs of motor units are spread throughout muscle •One motor unit has an action potential - gentle contraction of whole muscle •Two motor units - stronger contraction of whole muscle •The more motor units are recruited, the stronger the contraction
sarcoplasmic reticulum (SR)
•System of tubular sacs similar to smooth ER •Forms enlarged spaces - terminal cisterns where transverse tubules invaginate into sarcoplasm •Stores Ca++ in a relaxed muscle •Release of Ca++ triggers muscle contraction
Role of ATP in the Contraction Cycle
•The binding of myosin to actin releases chemical energy that has been stored in the tilted myosin heads •Stored energy is released when myosin binds to actin causing the head to pivot at the hinge region, returning the head to the inactivated position •The energy from the dephosphorylation of ATP is now spent and ADP and iP breaks away from myosin head •*The heads of activated myosin were tilted backward at ~ a 1100 angle to its tail •*Heads of inactivated myosin is tiled forward at ~ a 600 angle •The movement of the myosin head acts to pull the actin filament towards the center of the sarcomere, shortening the sarcomere •The inactivated myosin immediately captures another ATP and reactivates to continue the contraction cycle *angle measurements are estimated
Synapse at the NMJ
•The neurotransmitter at the NMJ is acetylcholine (ACh) •Neural impulses (action potentials) to control skeletal muscle originate in the primary motor cortex and flow through a neural pathway down the spinal cord to a motor neuron that carries the impulse to the NMJ of a muscle fiber •The effect of the neural action potential on the synaptic bulbs causes the release of ACh, by exocytosis, into the synaptic cleft at the NMJ •ACh diffuses across the synapse and binds to ACh receptors on the motor end plate; •ACh receptors are ligand gated Na+ channels. ACh is the ligand for the ligand this for this receptor •Binding of ACh to its receptors causes the opening of ligand-gated Na+ channels on the sarcolemma •Na+ floods through the open channels and flows along the inner surface of sarcolemma •Sarcolemma is depolarized; the neural action potential, representing a command to contract that originated in the brain, has been transmitted to the muscle fiber and results in an action potential in the muscle fiber •Ach remaining in the synaptic cleft is broken down by AChE
The Proteins of Myofibrils - Myosin
•Thick filaments are composed of myosin -each molecule resembles two golf clubs twisted together -myosin heads extend toward the thin filaments forming a cross bridge to the thin filament, (called cross bridges) -myosin heads connect to tail with a hinge region that allows movement as do the hinges that hold up a door
The Proteins of Myofibrils - Actin
•Thin filaments are composed of actin, troponin, and tropomyosin •G-actin - a globular protein with a spherical shape; each G-actin molecule has a binding site to which myosin can bind. There is a strong attraction between myosin and G-actin at this site. •F-actin - strands of G-actin molecules strung together to form a myofilament •In relaxed muscle fiber, the myosin-binding site on actin molecules is covered by tropomyosin, preventing myosin from binding to actin
The Proteins of Myofibrils - Titin
•Titan anchors thick filament to the M line and the Z line. It attaches to the proteins forming the Z line and extends towards the center of the sarcomere, going under the thick filaments and attaching to the M line •Titan is highly elastic; it can stretch to four times its resting length and recoil to its original length
Tropomyosin and Troponin
•Tropomyosin is a double stranded thread-like molecule •Troponin consists of three globular subunits: -One subunit binds to tropomyosin forming a troponin-tropomyosin complex -The second subunit binds to one G actin molecule in the F actin filament holding the troponin-tropomyosin complex in place -The third subunit has a binding site for two Ca++
Twitch Contraction
•Twitch contraction is a single stimulus-contraction-relaxation sequence in a muscle fiber •Timing of twitch contractions differs in different muscles •The stimulus that begins the twitch is the onset of the action potential in the muscle fiber •Myogram is a graph of a twitch contraction
Summation and Tetanus
•Wave summation, complete and incomplete tetanus primarily result from residual Ca++ in the sarcoplasm, open K+ channels and sarcomeres that are already partially contracted •Incomplete Tetanus: -Rapid cycles of contraction and slight relaxation of muscle fibers cause maximal contraction as the strength of each contraction builds on the previous one (summation, effects of one added to the next) -Can continue for relatively long period of time because fibers can relax and regenerate in between stimuli -Even when maximally contracted, all muscle fibers in a muscle do not all contract and relax in unison; some are recruited later or sooner, multiple motor neurons each sending stimuli at different rates and each neuron stimulates fibers that scatters throughout the muscle; at any point, some fibers are relaxed and other contracted. •Complete Tetanus: -Stimuli arrive so rapidly that the relaxation period is eliminated -Results in a prolonged and severe contraction that depletes muscle fibers of resources -Muscle fibers essentially collapse from exhaustion, serious implications for muscles and muscle fibers •Bacterial Tetanus caused by Clostridium tetani -C. tetani requires low oxygen levels; usually caused by deep puncture wounds that allow bacteria to penetrate the epidermis and upper dermis; wounds that seldom bleed freely and clean out wound -Bacteria produces a toxin that that severely impedes the normal functioning of motor neurons that control muscles through the body -40 - 60% mortality rate -Vaccine •Botulism caused by Clostridium botulinum -Bacteria produces a toxin that paralyzes muscles by preventing the release of ACH at neuromuscular junctions -Contaminated food products. Cooking at temperatures for long periods does nothing to prevent disease. This will kill the bacteria, but it is not the bacteria that causes disease. It is the toxin the bacteria produced.
