Chapter 6: Muscle
Events that occur at the neuromuscular junction - 5 & 6
5) ACh binding opens chemically gated ion channels that allow simultaneous passage of Na+ into the muscle fiber and K+ out of the muscle fiber. More Na+ ions enter than K+ ions exit, which produces a local change in the membrane potential called the end plate potential 6) ACh effects are terminated by its breakdown in the synaptic cleft by acetylcholinesterase and diffusion away from the junction
Muscle Tone
A phenomenon in which relaxed muscles are almost always slightly contracted due to spinal reflexes that activate first one group of motor units and then another in response to activated stretch receptors in the muscles
Striations
A repeating series of: - Dark (A) band: • Each dark A band has a lighter region in its midsection called the H zone. • Each H zone is bisected vertically by a dark line called the M line formed by myomesin. - Light (I) band: • has a midline darker area called the Z disc (or Z line)
When a nerve impulse reaches a neuromuscular junction, ___ is released. Upon binding to sarcolemma receptors, ___ causes a change in sarcolemma permeability motor neuron leading to a change in ____________ _____________
ACh; membrane potential
Generation of an Action Potential across the Sarcolemma (From EPP to the sarcolemma)
AP sweeps along the entire surface of the sarcolemma in three steps: Three steps are involved in triggering and then propagating an action potential: 1. Generation of end plate potential (EPP) 2. Action potential depolarization: once initiated → unstoppable 3. Repolarization: refractory period (no stimulation till repolarization is complete) to restore the ionic conditions (ATP-dependent Na-K pump) AP lasts a few milliseconds (ms), but the contraction phase of a muscle fiber may persist for > 100 ms
This cycle will continue as long as
ATP is available and Ca2 is bound to troponin. If ATP is not available, the cycle stops between steps 2 and3
intermittent claudication
("limping") occurs in some individuals. This condition restricts blood delivery to the legs, leading to excruciating pains in the leg muscles during walking, which forces the person to stop and rest
Skeletal muscle fibers contain two sets of intracellular tubules that help regulate muscle contraction:
(1) the sarcoplasmic reticulum and (2) T tubules.
Myofibril structure
- A rodlike structure that run parallel to muscle fiber 1-2 μm in diameter - Myofibrils are densely packed, forming 80% of cell volume, squeezing other organelles between them.
different pathways during during activities?
- Activities that require a surge of power but last only a few seconds, such as weight lifting, diving, and sprinting, rely entirely on ATP and CP stores. - The slightly longer bursts of activity in tennis, soccer, and a I00-meter swim appear to be fueled almost entirely by anaerobic glycolysis - Prolonged activities such as marathon runs and bicycle touring, where endurance rather than power is the goal, depend mainly on aerobic respiration using both glucose and fatty acids as fuels.
Which pathways predominate during exercise?
- As long as a muscle cell has enough oxygen, it will form ATP by the aerobic pathway - However, when exercise demands begin to exceed the ability of the muscle cells to carry out the necessary reactions quickly enough, anaerobic pathways begin to contribute more and more of the total ATP generated - Aerobic endurance: the length of time a muscle can continue to contract using aerobic pathways - Anaerobic threshold: point at which muscle metabolism converts to anaerobic glycolysis
Direct phosphorylation of ADP
- As we begin to exercise vigorously, the demand for ATP soars and the ATP stored in working muscles is consumed within a few twitches. - Then creatine phosphate (CP), a unique high-energy molecule stored in muscles, is tapped to regenerate ATP while other metabolic pathways adjust to the sudden high demand for ATP - Creatine phosphate+ ADP --> creatine + ATP - Oxygen use: None; Products: 1 ATP per CP, creatine; Duration of energy provided: 15 seconds - Cells store 2-3 times more CP than ATP
Anatomy of Motor Neurons and the Neuromuscular Junction: Motor (somatic) neurons
- Convey the "voluntary" order from the central nervous system to the skeletal muscles. • Cell body in the CNS and an axon extends (axons together form a nerve) to the muscle fiber. • As it enters the muscle, the axon of each motor neuron branches profusely to innervate multiple muscle fibers. • On the muscle fiber, the axon divides again, giving off several short, curling branches that collectively form an oval neuromuscular junction, or motor end plate, so that each muscle fiber has only one neuromuscular junction, located approximately midway along its length
Depolarization: Generating and propagating an action potential (AP)
- Depolarization of the sarcolemma opens voltage-gated sodium channels. - Na+ enters, following its electrochemical gradient. At a certain membrane voltage, an AP is generated (initiated). - The AP spreads to adjacent areas of the sarcolemma and opens voltage-gated Na+ channels there, propagating the AP. - The AP propagates along the sarcolemma in all directions, just like ripples from a pebble dropped in a pond
Attachments can be direct or indirect:
- Direct, or fleshy attachments, the epimysium of the muscle is fused to the periosteum of a bone or perichondrium of a cartilage. - Indirect attachments: the muscle's connective tissue wrappings extend beyond the muscle as a ropelike tendon or as a sheetlike aponeurosis, to the bone or cartilage or to fascia (CT covering) of other muscles. • Indirect attachments are more common because of their durability (strong enough to transmit force) and small size (conserve space at joints)
To remain healthy, muscles must be active. Immobilization due to enforced bed rest or loss of neural stirnulation results in
- Disuse atrophy (degeneration and loss of mass), which begins almost as soon as the muscles are immobilized. - Under such conditions, muscle strength can decline at the rate of 5% per day! - Even at rest, muscles continually receive weak stimuli - When totally deprived of neural stimulation, a paralyzed muscle may atrophy to one-quarter of its initial size. - Fibrous connective tissue replaces the lost muscle tissue, and complete recovery usually takes longer than the period of immobilization.
Explain the reason for this rigor moris rigidity
- Dying cells are unable to exclude calcium (which is in higher concentration in the extracellular fluid), and the calcium influx into muscle cells promotes formation of myosin cross bridges. - Shortly after breathing stops, ATP synthesis ceases, but ATP continues to be consumed and cross bridge detachment is impossible once all of the ATP is gone. - Actin and myosin become irreversibly cross-linked, producing the stiffness of rigor mortis, which gradually disappears as muscle proteins break down after death
Aerobic respiration
- Energy source: glucose; pyruvic acid; free fatty acids from adipose tissue; amino acids from protein catabolism - Glucose (from glycogen breakdown or delivered from blood) -> Pyruvic acid -> Aerobic respiration in mitochondria -> 32 ATP per glucose, CO2, H2O - Oxygen use required - Initially, muscle glycogen is used, then blood-born glucose, pyruvate from glycolysis and fatty acids but after 30 minutes fatty acids are the main source -Slow compared to anaerobic (takes hours)
Anaerobic glycolysis
- Glycolysis and Lactic Acid Formation - During glycolysis, glucose is broken down to two pyruvic acid molecules, releasing enough energy to form small amounts of ATP (2 ATP per glucose) - This pathway occurs in both the presence and the absence of oxygen, but because it does not use oxygen, it is an anaerobic - When blood flow and oxygen delivery are impaired during vigorous muscle contraction, most of the pyruvic acid is converted into lactic acid -In liver: lactic acid can be used as a source of energy (pyruvic acid, glucose) or stored in muscles as glycogen -2 ½ times faster than aerobic pathway but less ATP is produced
Velocity and Duration of Contraction (how long a muscle can contract before fatigue) influenced by:
- Muscle fiber type, - Load, and recruitment: • More load → slow and brief shortening, • More recruitment → more velocity & prolonged contraction.
Muscle fiber and Sarcoplasm structures
- Muscle fiber: is a long cylindrical multinucleated cell surrounded by the sarcolemma, with 10-100 μm diameter and up to 30 cm long. - Sarcoplasm: like cytoplasm but contains more glycosomes (granules of glycogen → glucose → ATP production) and myoglobin (red pigment stores oxygen)
Muscular dystrophy
- Refers to a group of inherited muscle destroying diseases that generally appear during childhood. - The affected muscles initially enlarge due to deposits of fat and connective tissue, but the muscle fibers atrophy and degenerate
Motor Neurons and muscles are excitable cells
- Respond to external stimuli by changing their resting membrane potential causing an action potential "AP" or nerve impulse). • AP can spread along the membrane of the cell • For AP to spread from cell to another cell: gap-junction or by neurotransmitters (across a gap) acting on receptors
Regular exercise helps
- Reverse sarcopenia, and frail elders who begin to "pump iron" (lift leg and hand weights) can rebuild muscle mass and dramatically increase their strength. - Performing those lifting exercises rapidly can improve our ability to carry out the "explosive" movements needed to rise from a chair. - Even moderate activity, like taking a walk daily, improves neuromuscularfunction and enhances independent living.
Triad Relationships
- T tubules and SR have membrane-spanning proteins across the gap between the two membranes: • The protruding integral proteins of the T tubule act as voltage sensors. • The integral proteins of the SR form gated channels through which the terminal cisterns release Ca2+
Muscle Response to Changes in Stimulus Frequency:
- Temporal or wave summation: when a second muscle twitch rides on the first muscle twitch due to two successive (identical) stimuli, the second twitch will be stronger than the first, because the second contraction begins before the muscle has completely relaxed. • In other words, contractions are added (more Ca is available in the sarcoplasm). • If a second stimulus arrives before repolarization is complete, no wave summation occurs.
Skeletal muscle contraction: step 3
- The AP in the sarcolemma propagates along the T tubules and causes release of Ca2+ from the tenninal cisterns of the SR. - Ca2+ is the final trigger for contraction. It is the internal messenger that links the AP to contraction. - Ca2+ binds to troponin and this causes the myosin-binding sites on actin to be exposed so that myosin heads can bind to actin.
As we age
- The amount of connective tissue in our skeletalmuscles increases, the number of muscle fibers decreases, and the muscles become stringier, or more sinewy. - By age 30, even in healthy people, a gradual loss of muscle mass, called sarcopenia, begins. - Because skeletal muscles form so much of the body mass, body weight and muscle strength decline in tandem.
Define motor unit
- The motor unit consists of one motor neuron and all the muscle fibers it innervates so that when a motor neuron fires, all the muscle fibers it innervates contract. - The number of muscle fibers per motor unit depends on the purpose of the muscle: few in muscles that exert fine control (fingers and eyes) and large in large, weight-bearing less precise muscles (hip muscles) - The fibers of a motor unit are not isolated from the rest of the muscle (so a single motor unit causes a weak but uniform contraction of the muscle)
Repolarization: Restoring the sarcolemma to its initial polarized state (negative inside, positive outside)
- The repolarization wave is also a consequence of opening and closing ion channels-voltage-gated Na+ channels close and voltage-gated K+ channels open. - The potassium ion concentration is substantially higher inside the cell than in the extracellular fluid, so K+ diffuses out of the muscle fiber. - This restores the negatively charged conditions inside that are characteristic of a sarcolemma at rest.
Graded Muscle Contraction
- This is a sort of healthy muscle contraction that is relatively smooth and varies in strength based on demand reflecting a proper control of skeletal movement - This can be achieved by two ways: • An increase in the frequency of stimulation causes temporal summation (greater contraction strength) of a given motor unit. • An increase in the strength of stimulation causes recruitment (more motor units into action)
The aftermath of E-C Coupling
- When the muscle AP ceases, the voltage-sensitive tubule proteins return to their original shape, closing the Ca2+ release channels of the SR. - Ca2+ levels in the sarcoplasm fall as Ca2+ is continually pumped back into the SR by active transport. - Without Ca2+, the blocking action of tropomyosin is restored, myosin-actin interaction is inhibited, and relaxation occurs. - Each time an AP arrives at the neuromuscular junction, the sequence of E-C coupling is repeated.
Smooth Muscle
- elongated cells, non-striated, involuntary, slow sustained contraction - in the walls of hollow visceral organs, (stomach, urinary bladder, and respiratory passages), - forces fluids and other substances through internal body channels, - forms valves controlling internal body openings, dilates and constricts the pupils of eyes, and forms the arrector pili muscles
isotonic contraction
- increasing in muscle tension can overcome the load leading to change in length (contraction), so the tension stays the same for a certain load. - concentric (works by shortening, biceps curl "flexion") and eccentric (works by lengthening, forceful and needs more energy, walking down hill or "extension" of a biceps curl)
cross-bridge cycle
- repeated sequential interactions between myosin and actin filaments at cross-bridges that cause a muscle fiber to contract - is the series of events during which myosin heads pull thin filaments toward the center of the sarcomere
The cross bridge cycle is the series of events during which myosin heads pull thin filaments toward the center of the sarcomere:
1. Cross bridge formation. Energized myosin head attaches to an actin myofi lament, forming a cross bridge 2. The power (working) stroke. ADP and P; are released and the myosin head pivots and bends, changing to its bent low-energy state. As a result it pulls the act in filament toward the M line 3. Cross bridge detachment . After ATP attaches to myosin, the Iink between myosin and actin weakens, and the myosin head detaches (the cross bridge "breaks") 4. Cocking of the myosin head. As myosin hydrolyzes ATP to ADP and P., the myosin head returns to its prestroke high-energy, or "cocked," position
Three pathways of ATP re/generation in the muscle:
1. Direct phosphorylation of ADP by creatine phosphate (high energy molecule stored in muscles) 2. Anaerobic glycolysis, which converts glucose to lactic acid 3. Aerobic respiration
Myoblasts fuse to form a multinucleate skeletal muscle fiber
1. Embryonic mesoderm cells called myoblasts undergo celI division (to increase number) and enlarge 2. Several myoblasts fuse together to form a myotube 3. Myotube matures into skeletal muscle fiber
Every twitch myogram has three distinct phases:
1. Latent period: first few milliseconds following stimulation when the excitation-contraction coupling is occurring but muscle tension is not yet measurable 2. Period of contraction: cross bridges are active, from the onset to the peak of tension development (10-100 ms) 3. Period of relaxation: 10-100ms, due to pumping of Ca2+ back into the SR → ↓cross-bridges and contractile force declines, muscle tension decreases to zero (baseline)
Influence of load on duration and velocity of muscle shortening
Because muscles are attached to bones, they are always pitted against some resistance, or load, when they contract. As you might expect, they contract fastest when there is no added load on them. A greater load results in a longer latent period, slower shortening, and a briefer duration of shortening
STRUCTURE AND ORGANIZATIONAL LEVEL: Myofilament, or filament (extended macromolecular structure)
DESCRIPTION: - Contractile myofilaments are of two typesthick and thin. - Thick fiilaments contain bundled myosin molecules; thin filaments contain actin molecules (plus other proteins). - The sliding of the thin filaments past the thick filaments produces muscle shortening. - Elastic filaments (not shown here) provide elastic recoil when tension is released and help maintain myofilament organization.
STRUCTURE AND ORGANIZATIONAL LEVEL: Fascicle
DESCRIPTION: A fascicle is a discrete bundle of muscle cells, segregated from the rest of the muscle by a connective tissue sheath. CONNECTIVE TISSUE WRAPPINGS: Surrounded by perimysium
STRUCTURE AND ORGANIZATIONAL LEVEL: Muscle (organ)
DESCRIPTION: A muscle consists of hundreds to thousands of muscle cells, plus connective t issue wrappings, blood vessels, and nerve fibers. CONNECTIVE TISSUE WRAPPINGS: Covered externally by the epimysium
STRUCTURE AND ORGANIZATIONAL LEVEL: Muscle fiber (cell)
DESCRIPTION: A muscle fiber is an elongated multi nucleate cell; it has a banded (striated) appearance. CONNECTIVE TISSUE WRAPPINGS: Surrounded by endomysium
STRUCTURE AND ORGANIZATIONAL LEVEL: Sarcomere (a segment of a myofibril)
DESCRIPTION: A sarcomere is the contractile unit, composed of myofilaments made up of contractile proteins.
STRUCTURE AND ORGANIZATIONAL LEVEL: Myofibril (complex organelle composed of bundles of myofilaments)
DESCRIPTION: Myofibrils are rodlike contractile elements that occupy most of the muscle cell volume. Composed of sarcomeres arranged end to end, they appear banded, and bands of adjacent myofibrils are aligned.
The trough-like part of the muscle fiber's sarcolemma that helps form the neuromuscular junction is highly folded - why?
These junctional folds provide a large surface area for the thousands of ACh receptors located there
Skeletal Muscle
Voluntary, striated (striped), attached to and cover the skeleton, moves the skeleton, contracts rapidly, tires easily, exerts tremendous power.
Ion Channels needed to
allow certain ions to pass across the membrane to change the membrane voltage (spreading the AP)
Myasthenia gravis
an autoimmune disease destroying ACh receptors causing drooping upper eyelids, difficulty swallowing and talking, and generalized muscle weakness
Motor units are more commonly activated ________________
asynchronously; some contract while others relax to prevent fatigue and produce smooth contraction
Each muscle fiber has only one neuromuscular junction, located approximately midway along its length. The end of the axon is called
axon terminal
Sarcomeres structure
building (functional) contractile unites of the myofibrils, ∼ 2 μm long, between 2 successive Z discs which contain smaller rodlike structures called myofilaments
Temporal summation contributes to
contractile force and primarily to produce smooth, continuous muscle contractions by rapidly stimulating a specific number of muscle cells
ATP is the only direct source that supplies
energy to move and detach cross bridges, operate the calcium pump in the SR, and operate the Na+-K+ pump in the plasma membrane
Myoblasts producing cardiac and smooth muscle cells do not fuse but develop ___ ____________ at a very early embryonic stage. Cardiac muscle is pumping blood just _ weeks after fertilization
gap junctions; 3
Connective Tissue Sheaths
hold together and wrap around individual muscle fibers; support each cell and reinforce the muscle as a whole
isometric contraction
increasing the muscle tension is less than the load, so no change in the length but tension builds up, examples: maintain upright posture or to hold joints stationary while movements occur at other joints
When nerve impulses arrive in quick succession
intracellular Ca2+ levels soar due to successive "puffs" of Ca2+ from the SR → no complete relaxation between stimuli → stronger and sustained contraction
Muscle fatigue
is a state of physiological inability to contract even though the muscle is still receiving stimuli
The neuromuscular junction
is the region where the motor neuron contacts the skeletal muscle. It consists of multiple axon terminals and the underlying junctional folds of the sarcolemma.
if stimulation frequency continues to increase,
muscle tension reaches maximal (relaxation disappears) and the contractions fuse into a smooth, sustained contraction plateau called fused or complete tetanus (rarely if ever occurs)
With rare exceptions, all three types of muscle tissue develop from cells called
myoblasts that arise from the embryonic mesoderm
Specialized Organelles
myofibrils, sarcoplasmic reticulum, and T tubules
Cardiac Muscle
only in the heart, striated, not voluntary. neural controls allow the heart to speed up for brief periods.
we can classify skeletal muscle cells as
slow oxidative fibers, fast oxidative fibers, or fast glycolytic fibers
Within the moundlike axon terminal are
synaptic vesicles, small membranous sacs containing the neurotransmitter acetylcholine (ACh)
EPOC represents the difference between
the amount of oxygen needed for totally aerobic muscle activity and the amount actually used. All anaerobic sources of ATP used during muscle activity contribute to EPOC.
Excess Postexercise Oxygen Consumption (EPOC, formerly called oxygen debt)
the extra amount of O2 that the body needs to take after stopping the exercise, to restore the muscle conditions to pre-exercise state
So the brain decides
the rate of AP firing on the motor neuron AND the number of motor neurons to be activated
the axon terminal, and the muscle fiber are exceedingly close, but they remain separated by a space called
the synaptic cleft, which is filled with a gel-like extracellular substance rich in glycoproteins and collagen fibers
Myofibril arrangement:
• A hexagonal arrangement of six thin filaments surrounds each thick filament and, • Three thick filaments enclose each thin filament. • The H zone of the A band is less dense because the thin filaments do not extend into this region. • The M line in the center of the H zone is slightly darker because of accessory proteins holding thick filaments • The myofilaments are held in alignment at the Z discs and the M lines, and are anchored to the sarcolemma at the Z discs.
Thin filaments
• Actin: globular actin or G actin (kidney-shaped polypeptide subunits each has a binding site for myosin). G actin polymerize into two long actin filaments called filamentous, or F, actin twisted together • Polypeptide strands of tropomyosin: a rod-shaped protein, spiral about the actin core to stabilize it, and block myosin-binding sites on actin during relaxation • Troponin: a globular protein with three polypeptide subunits: One attaches troponin to actin, the 2nd binds tropomyosin to actin, and the 3rd binds calcium ions.
Sarcoplasmic Reticulum (SR)
• An elaborate smooth endoplasmic reticulum for Ca+ level regulation (storage & release) which is important for contraction. • Several SRs surround longitudinally each myofibril, communicating with each other at the H zone. • Paired terminal cisterns ("end sacs") form larger, perpendicular cross channels at the A band-I band junctions, • Large numbers of mitochondria and glycogen granules (providing energy) lie close to SR
Describe the steps of a cross-bridge cycle
• As Ca2+ levels rise, 2 Ca2+ bind to troponin which changes shape and rolls tropomyosin away from the myosin binding sites. • Once binding sites on actin are exposed, the events of the cross-bridge cycle occur in rapid succession • The thin filaments continue to slide as long as calcium and adequate ATP are present. • The thin filaments cannot slide backward because some myosin heads are always in contact with actin. • Contracting muscles shorten by 30-35% of their total resting length.
Cross-bridge cycle - Muscle relaxation
• As soon as Ca2+ is released, the Ca2+ pumps of the SR begin to reclaim it from the cytosol. • As Ca2+ levels drop, Ca2+ leave troponin, which again changes shape and pulls tropomyosin up to block actin's myosin-binding sites → relaxation
Compare eye muscles to calf muscles
• Contraction is usually faster than relaxation • Speed of contraction depends on the muscle's purpose (location) reflecting variations in enzymes and metabolic properties • Twitch contractions of some muscles are rapid and brief, as with the extraocular muscles controlling eye movements. In contrast, the fibers of fleshy calf muscles (gastrocnemius and soleus) contract more slowly and remain contracted for much longer periods. These differences between muscles reflect variations in enzymes and metabolic properties of the myofibrils.
T Tubules
• Deep tubule-like protrusions of the sarcoplasm at each junction between A & I bands • The lumen (cavity) of the T tubule is continuous with the extracellular space (so these tubules increase the muscle fiber surface area and help to convey the depolarization deep into the muscle fiber). • Each T tubule runs between the paired terminal cisterns of the SR, forming triads (2 terminal cisterns + T tubule) encircling each sarcomere. • So when the nerve impulse reaches the sarcolemma, distribute to the T-tubules which activates the release of Ca from the adjacent terminal cisterns into each sarcomere
Connective Tissue Sheaths: From external to internal
• Epimysium: "overcoat" of dense irregular CT surrounding the whole muscle, blends with the deep fascia between muscles or the superficial fascia deep to the skin • Perimysium and fascicles: muscle fibers are grouped into fascicles, each surrounded a layer of dense irregular CT called perimysium • Endomysium: a wispy sheath of fine areolar CT that surrounds each individual muscle fiber. All these sheaths are continuous with one another as well as with the tendons that join muscles to bones.
Characteristics of Muscle Tissue
• Excitability, or responsiveness is the ability of a cell to receive and respond to a stimulus (neurotransmitter) by changing its membrane potential. • Contractility is the ability to shorten forcibly when adequately stimulated • Extensibility is the ability to extend or stretch. • Elasticity is the ability of a muscle cell to recoil and resume its resting length after stretching.
Muscle Fiber Type: classified into:
• Fast or slow: according to speed of contraction (how fast myosin ATPase can split ATP and electrical activity of their neurons) and contraction duration (how fast Ca ions move from cytosol to SR) • Oxidative or glycolytic according to the major pathways for forming ATP: oxygen-using aerobic pathways for ATP (oxidative fibers) vs anaerobic glycolysis and creatine phosphate dependent fibers (glycolytic fibers)
Muscle fatigue in general:
• Intense short exercise produces fatigue rapidly, but recovery is rapid. • Prolonged low-intensity exercise causes slow developing fatigue, but recovery is delayed
• Causes (chemical changes) of fatigue that alter excitation-contraction coupling:
• Ionic imbalances: K+ is lost from the cells and Na+ is gained, disturbing the membrane potential and weakening the action potential → ↓ voltage sensitive ion channels in T-tubules→ ↓ calcium release from SR. • Increased inorganic phosphate (Pi) from CP and ATP breakdown may interfere with the release of Ca from the SR and Pi from myosin → ↓ power strokes. • Decreased ATP and increased magnesium (Mg2+) which act on the voltage sensitive proteins in the T tubule to decrease Ca2+ release from the SR. • Decreased glycogen and accumulation of lactic acid in the muscle (soreness of muscle during exercise)
Electrochemical and mechanical events occurring within a muscle are identical in both contractions, however:
• Isotonic: filaments slide • Isometric: no sliding of filaments but but cross-bridges generate force without sliding (keep the relaxing length but with active cross bridges)
For a muscle to return to its pre-exercise state, the following must occur:
• Its oxygen reserves (stored in myoglobin) must be replenished. • The accumulated lactic acid must be reconverted to pyruvic acid (by liver). • Glycogen stores must be replaced. • ATP and creatine phosphate reserves must be resynthesized.
Basic Terms:
• Muscle fiber: Skeletal and smooth muscle cells (not cardiac muscle cells) are elongated • Myo-, mys- or sarco-: reference is to muscle. • Sarcolemma: muscle plasma membrane • Sarcoplasm: cytoplasm of muscle cells.
Each skeletal muscle is a discrete organ, has:
• Muscle fibers • Blood vessels (artery and vein): enter through the center of the muscle and divide profusely (rich capillary network) to meet the tremendous energy needed and clear the waste • Nerve: enters also at the center, one nerve ending to each fiber
Thick filaments
• Myosin: each molecule consists of six polypeptide chains: two heavy chains (twisting together forming the rodlike tail that ends as a globular head with flexible hinge) and four light chains (associated with the globular head). • The globular heads link the thick and thin filaments together, forming cross bridges, to generate force. • Myosin itself splits ATP (acts as an ATPase) and uses the released energy to drive movement. • The central portion of a thick filament (in the H zone) is smooth, but its ends shows myosin heads.
A muscle has two attachments to the nearby bones:
• Origin: is the least movable or immovable attachment (in limbs usually lies proximal) • Insertion: the attachment that moves to towards the origin
Muscle Functions:
• Produce movement: locomotion and manipulation, avoid injury, emotional expression, blood pressure control, movement of substances (foodstuffs, urine, semen) • Maintain posture and body position. • Stabilize joints • Generate heat
Describe the sliding filament model of muscle contraction 1
• Shortening only occurs if the cross bridges generate enough tension on the thin filaments to exceed the forces that oppose shortening, • Contraction ends when the cross bridges become inactive, to relax. • In a relaxed muscle fiber, the thin and thick filaments overlap only at the ends of the A band. • The sliding filament model of contraction states that during contraction, the thin filaments slide past the thick ones so that the actin and myosin filaments overlap to a greater degree. Neither the thick nor the thin filaments change length during contraction.
Regarding muscle regeneration
• Skeletal muscles stop dividing early on. However, satellite cells, myoblast-like cells associated with skeletal muscle, help repair injured fibers and allow limited regeneration of dead skeletal muscle, a capability that declines with age. • Cardiac muscle was thought to have no regenerative capability whatsoever, but recent studies suggest that cardiac cells do divide, but only at about I% per year. As a result, injured heart muscle is repaired mostly by scar tissue. • Smooth muscles have a good regenerative capacity, and smooth muscle cells of blood vessels divide regularly throughout life
Describe the sliding filament model of muscle contraction at the microscopic level
• The I bands shorten. • The distance between successive Z discs shortens (Z-lines pulled towards the M-line). • The H zones disappear. • The contiguous A bands move
Other proteins
• The elastic filament; titin helps in recoil and resist excessive stretching • Dystrophin: which links the thin filaments to the integral proteins of the sarcolemma • Other proteins (nebulin, myomesin and C proteins): bind filaments or sarcomeres together. • Intermediate (desmin) filaments: extend from the Z disc and connect myofibrils together
Length-tension relationship (isometric contraction):
• The ideal length on this curve occurs when the muscle is close to its resting length and the thin and thick filaments overlap optimally • If a muscle is stretched so much that the filaments do not overlap, the myosin heads have nothing to attach to and cannot generate tension. • If the sarcomeres are so compressed, little or no further shortening can occur. - Skeletal muscles are maintained near their optimal resting length and Joints normally limit bone movements to prevent overstretch of the attached muscles.
The recruitment process is dictated by the size principle:
• The motor units with the smallest muscle fibers are activated first because they are controlled by the smallest, most highly excitable motor neurons. • Motor units with larger muscle fibers begin to be excited, contractile strength increases. • The largest motor units, containing large, coarse most powerful muscle fibers, are controlled by the largest, least excitable (highest threshold)
Two facts about muscle mechanics:
• The principles governing the contraction of a single muscle fiber and of a skeletal muscle are the same. • The force exerted by a contracting muscle on an object is called muscle tension and the opposing force exerted on the muscle by the weight of the object to be moved is called the load.
If the muscle is stimulated at an increasingly faster rate:
• The relaxation time between twitches becomes shorter. • Ca2+ concentration in the cytosol rises higher. • Wave summation becomes greater → sustained but quivering contraction called unfused or incomplete tetanus
Excitation-Contraction (E-C) Coupling
• The sequence of events by which transmission of an AP along the sarcolemma causes myofilaments to slide. • The AP is brief and ends well before any signs of contraction are obvious. • The electrical signal does not act directly on the myofilaments. • AP causes a rise in the intracellular levels of calcium ions, which triggers sliding of the filament.
Describe the sliding filament model of muscle contraction 2
• When the nervous system stimulates muscle fibers, the myosin heads on the thick filaments latch onto myosin-binding sites on actin in the thin filaments, and the sliding begins. • These cross bridge attachments form and break several times during a contraction, acting like tiny ratchets to generate tension and propel the thin filaments toward the center of the sarcomere. • As this event occurs simultaneously in sarcomeres throughout the cell, the muscle cell shortens.
Muscle Tone does not produce active movements, but
• keeps the muscles firm, healthy, and ready to stimulation. • helps stabilize joints and maintain posture
Skeletal muscle contraction: step 1
Events at the neuromuscular junction. The motor neuron releases ACh that stimulates the skeletal muscle fiber, causing a local depolarization (decrease in membrane potential) called an end plale potential (EPP).
FOUR factors control the force of skeletal muscle contraction:
Frequency of stimulation, Number of muscle fibers recruited, Size of muscle fibers, Degree of muscle stretch (The tension the muscle can generate varies with its pre-contraction length)
A muscle twitch is
In the laboratory, a muscle twitch is the response of a muscle to a single stimulation (quick contraction and then relaxation)
Why is the size principle important?
It allows the increases in force during weak contractions (to maintain posture or slow movements) to occur in small steps, whereas gradations in muscle force are progressively greater when large amounts of force are needed for vigorous activities such as jumping or running
Myofilaments
Orderly arranged contractile filaments of two types: • The central thick filaments: containing myosin, extend the entire length of the A band, connected at the M line by accessory proteins • The lateral thin filaments: containing actin (mainly), extend across the I band and partway into the A band • The Z disc: a protein sheet that anchors the thin (actin) filaments and the elastic filaments (that hold thick myosin filaments across the sarcomeres).
Muscle Response to Changes in Stimulus Strength
Recruitment , also called multiple motor unit summation, controls the force of contraction. In the lab, recruitment is achieved by delivering stimuli of increasing voltage, calling more and more muscle fibers: - Subthreshold stimuli: no response - Threshold stimulus: gives the first observable contraction • Beyond this, the muscle contracts more as the stimulus strength increases. - The maximal stimulus: the strongest stimulus that increases contractile force at which all the muscle's motor units are recruited. • In the lab, increasing the stimulus beyond the maximal stimulus does not produce a stronger contraction
In the absence of ATP, myosin heads will not detach, causing *rigor mortis*
Rigor Mortis (death rigor): Most muscles begin to stiffen 3 to 4 hours after death. Peak rigidity occurs at 12 hours and then gradually dissipates over the next 48 to 60 hours
Skeletal muscle contraction: step 2
The EPP triggers an action potential that travels across the entire sarcolemma
Events that occur at the neuromuscular junction - 1, 2, 3, 4
1) Action potential arrives at axon terminal of motor neuron. 2) Voltage-gated Ca2+ channels open. Ca2+ enters the axon terminal, moving down its electrochemical gradient. 3) Ca2 entry causes ACh (a neurotransmitter) to be released by exocytosis 4) ACh diffuses across the synaptic cleft and binds to ACh receptors on the sarcolemma.
Two types of ion channels
1. Chemically gated ion channels: • Both a receptor and an ion channel • Opened by chemical messengers (e.g., neurotransmitters, such acetylcholine, ACh). • Creates small local changes in the membrane potential 2. Voltage gated ion channels: • Open or close in response to AP (created by chemically gated channels) then help in spreading it.
Steps 1 and 2 in E-C Coupling
1. The action potential (AP) propagates along the sarcolemma and down the T tubules 2. Calcium ions are released. Transmission of the AP along the T tubules of the triads causes the voltage sensitive tubule proteins to change shape. This shape change opens the Ca2+ release channels in the terminal cisterns of the sarcoplasmic reticulum (SR, allowing Ca2+ to flow into the cytosol).
Steps 3 and 4 in E-C Coupling
3) Calcium binds to troponin and removes the blocking action of tropomyosin. When Ca2+ binds, troponin changes shape, exposing myosin-binding sites on the thin filaments. 4) Contraction begins: Myosin binding to actin forms cross bridges and contraction (cross bridge cycling) begins. At this point, E-C coupling is over.
On average, women's skeletal muscles makeup approximately ___ of body mass, whereas men's account for about ___ ]
36% 42% Body strength per unit muscle mass , however, is the same in both sexes.
Generation of end plate potential (EPP)
An end plate potential (EPP) is generated at the neuromuscular junction. The EPP causes a wave of depolarization that spreads to the adjacent sarcolemma.
The most common and serious form of muscular dystrophy is
Duchenne muscular dystrophy (DMD): • sex-linked recessive inherited disease, expressed exclusively in males (one in every 3600 male births, 2-7 years) and is diagnosed when the boy is between 2 and 7 years old • destroys limb muscles then ascend to trunk and heart • With supportive care, patients can live to 30s and beyond. • Caused by a defective gene for dystrophin making the sarcolemma fragile allowing entry of excess Ca2+ , which damages the contractile fibers with inflammation and loss of regenerative capacity.
By age 80
Muscle strength usually decreases by about 50%. This "flesh wasting" condition has serious health implications for the elderly, particularly because falling becomes a common event.
Skeletal muscle contraction: step 4
The muscle contracts as a result of a repeating cycle of steps that cause myofilaments to slide relative to each other
