Muscle Cells: Characteristics and Function

• Muscle cells in animals are specialized for movement.
• Skeletal muscle holds the body erect against gravity and produces visible movement.
• Muscle cells possess excitability, conductivity, contractility, extensibility, and elasticity.

Universal Characteristics of Muscle Cells

• Excitability is the responsiveness to stimuli, highly developed in muscle and nerve cells.
• Conductivity is the ability to transmit a wave of excitation along the cell, initiating muscle contraction.
• Contractility is the unique ability to shorten upon stimulation, enabling pulling on bones and organs.
• Extensibility allows muscle cells to stretch between contractions; skeletal muscle fibers can stretch up to three times their contracted length.
• Elasticity is the capacity to recoil to the original resting length after being stretched and then released.
• Skeletal muscle, also known as voluntary striated muscle, is typically attached to one or more bones.
• Skeletal muscle exhibits light and dark transverse bands called striations.
• It is called voluntary because it is usually subject to conscious control, unlike involuntary muscles that are never attached to bones.
• A typical skeletal muscle cell measures about 100 µm in diameter and 3 cm long, but can be as thick as 500 µm and as long as 30 cm.
• Due to their length, skeletal muscle cells are often referred to as muscle fibers or myofibers.
• Skeletal muscle is composed of muscular and fibrous connective tissue.

Connective Tissues in Skeletal Muscle

• The endomysium surrounds each muscle fiber.
• The perimysium bundles muscle fibers into fascicles.
• The epimysium encloses the entire muscle.
• These connective tissues are continuous with collagen fibers of tendons, which are continuous with the bone matrix collagen.
• Muscle collagen is neither excitable nor contractile but is somewhat extensible and elastic.
• Muscle collagen resists excessive stretching, protecting the muscle from injury during lengthening.
• Some believe tendon recoil contributes to power output and muscle efficiency, while others find human elasticity negligible.
• Muscle fiber has a complex internal structure closely tied to its contractile function.
• The plasma membrane of muscle fibers is the sarcolemma, and its cytoplasm is the sarcoplasm.

Sarcolemma and Sarcoplasm of Muscle Fibers

• The sarcoplasm contains mainly myofibrils (long protein cords about 1 µm n diameter), glycogen (starch-like carbohydrate for energy storage), and myoglobin (red pigment that binds oxygen).
• Muscle fibers have multiple flattened or sausage-shaped nuclei pressed against the inside of the sarcolemma.
• During embryonic development, myoblasts fuse to produce each multi-nucleated muscle fiber.
• Some myoblasts remain as unspecialized satellite cells between the muscle fiber and the endomysium, aiding in regeneration.
• Most organelles are packed into the spaces between myofibrils, including the sarcoplasmic reticulum (SR).

Muscle Fiber Organelles

• The sarcoplasmic reticulum (SR) is a network around each myofibril with dilated end-sacs called terminal cisternae.
• The sarcolemma features tubular infoldings called transverse (T) tubules that penetrate the cell and emerge on the other side.
• Each T tubule associates with two terminal cisternae, forming a triad.
• The sarcoplasmic reticulum stores calcium ions and has gated channels that release a flood of calcium into the cytosol to activate muscle contraction
• T tubules signal the SR to release calcium bursts.
• Each myofibril consists of parallel protein microfilaments called myofilaments, which exist in three forms.

Muscle Filaments

• Thick filaments are about 15 nm in diameter and made of several hundred myosin molecules.
• A myosin molecule resembles a golf club with two chains intertwined to form a shaft-like tail and a double globular head projecting at an angle
• Thick filaments are like bundles of golf clubs with heads directed outward in a helical array around the bundle and angle left on one half and those on the other half angle to the right, with a bare zone in the middle
• Thin filaments are 7 nm in diameter, composed of two intertwined strands of fibrous (F) actin.
• Each F actin strand is a string of globular (G) actin subunits, in which each G actin has an active site that binds to the head of a myosin molecule.
• A thin filament also contains 40 to 60 molecules of tropomyosin, which blocks active sites of G actins when the muscle fiber is relaxed.
• Troponin, a calcium-binding protein, is bound to every tropomyosin molecule.
• Elastic filaments, 1 nm in diameter, consist of the large protein titin.
• Elastic filaments run through the core of each thick filament, anchoring it to the Z disc at one end and the M line at the other, stabilizing the thick filament.
• Myosin and actin are called contractile proteins because they shorten the muscle fiber.
• Tropomyosin and troponin are called regulatory proteins because they determine when a fiber can contract.
• The action of these regulatory proteins depends on the availability of calcium ions, which bind to troponin.
• At least seven accessory proteins occur in thick and thin filaments or are associated with them; the most clinically important is dystrophin.

Dystrophin

• Dystrophin is a large protein located between the sarcolemma and outermost myofilaments.
• Dystrophin links actin filaments to a peripheral protein on the inner face of the sarcolemma, leading to the fibrous endomysium.
• When thin filaments move, they pull on dystrophin, which pulls on extracellular connective tissues leading to the tendon.
• Genetic defects in dystrophin lead to muscular dystrophy.
• Myosin and actin arrange in a precise array that accounts for the striations found in skeletal and cardiac muscle.
• Striated muscle has dark A (anisotropic) bands alternating with lighter I (isotropic) bands, based on their effect on polarized light.
• Each A band comprises thick filaments lying side by side, with part of it being especially dark, where each thick filament is surrounded by a hexagonal array of thin filaments.
• The middle of the A band has a light region called the H band, into which thin filaments do not reach.
• The thick filaments are linked by a dark, transverse protein complex called the M line in the middle of the H band.
• Each light I band is bisected by a dark narrow Z disc (Z line), which anchors thin and elastic filaments.
• A sarcomere is each segment of a myofibril from one Z disc to the next, and it is the functional contractile unit of the muscle fiber.
• Muscle shortens because its individual sarcomeres shorten and pull the Z discs closer together.
• Dystrophin and linking proteins pull on extracellular proteins of the muscle.
• Z discs pull on the sarcolemma to achieve overall cell shortening.

The Nerve-Muscle Relationship

• The relationship between nerve and muscle cells is important to understanding muscle contraction. Skeletal muscle never contracts unless stimulated by a nerve or artificially with electrodes.
• Somatic motor neurons, with cell bodies in the brainstem and spinal cord, stimulate muscle fibers via their axons (somatic motor fibers.)
• A single motor fiber and all the muscle fibers it innervates is collectively called a motor unit.
• The muscle fibers of a single motor unit are dispersed throughout a muscle, so that their stimulation causes a weak contraction over a wide area.
• On average, about 200 muscle fibers are innervated by each motor neuron, but can be smaller or larger to serve different purposes.
• Small motor units are present where fine control is needed, such as in the muscles of eye movement (3 to 6 muscle fibers per neuron).
• Large motor units are present where strength is more important than fine control, such as in the gastrocnemius (1,000 muscle fibers per neuron).
• Having multiple motor units allows them to work in shifts, so that when some units become fatigued, others can take over and the muscle as a whole can sustain long-term contraction.

Synapses

• A synapse is the point where a nerve fiber meets its target cell, and when the target cell is a muscle fiber, the synapse is called a neuromuscular junction (NMJ) or motor end plate.
• Each terminal branch of the nerve fiber has its own synapse with the muscle fiber, so one nerve fiber stimulates the muscle fiber at several points within the NMJ.
• At each synapse, the nerve fiber ends in a bulbous swelling called a synaptic knob, which is separated from the muscle fiber by a narrow space 60 to 100 nm wide called the synaptic cleft.
• A Schwann cell envelopes the entire junction.
• A synaptic knob contains spheroidal organelles called synaptic vesicles, which are filled with the neurotransmitter acetylcholine (ACh).
• ACh is released into the synaptic cleft when the nerve impulse reaches the nerve endings.
• The muscle fiber has about 50 million ACh receptors incorporated into its sarcolemma across from the synaptic knobs. In this area, the sarcolemma contains numerous infoldings called junctional folds, which increase the surface area of ACh-sensitive membrane.
• A deficiency of ACh receptors leads to the muscle paralysis of myasthenia gravis.
• The muscle fiber and the Schwann cell of the NMJ are surrounded by a basal lamina, which separates them from surrounding connective tissue and passes through the synaptic cleft.
• Both the sarcolemma and the basal lamina contain acetylcholinesterase (AChE), which breaks down ACh.
• Muscle and nerve cells are considered electrically excitable cells because their plasma membranes exhibit voltage changes in response to stimulation.
• The study of the electrical activity of cells is called electrophysiology.
• In an unstimulated (resting) cell, more anions (negative ions) are found on the inside of the plasma membrane than on the outside, therefore the membrane is polarized.

Electrical Signals In The Body

• In a resting muscle cell, Na+ is in excess in the extracellular fluid (ECF) and K+ is in excess in the intracellular fluid (ICF).
• Electrical potential, or voltage, is a difference in electrical charge between two points.
• The voltage across the sarcolemma of a muscle cell is about –90 mV called the resting membrane potential (RMP).
• The negative sign indicates a relatively negative charge on the intracellular side of the membrane.
• The sodium-potassium pump maintains the resting membrane potential.
• When a nerve or muscle cell is stimulated, ion channels in the plasma membrane open and Na+ flows into the cell down its electrochemical gradient.
• These Na+ cations override the negative charge just inside the membrane, and the inside of the membrane briefly becomes positive -- depolarization.
• The Na+ channels then close and K+ channels open; K+ rushes out of the cell (down its electrochemical gradient) and turns the inside of the membrane negative again -- repolarization.
• An action potential is the voltage shift of depolarization followed by repolarization.
• Action potentials perpetuate themselves along a membrane.
• A wave of action potential moving along a nerve fiber is a nerve impulse or nerve signal.

Skeletal Muscle Fibers

• The process of muscle contraction and relaxation has four major phases: excitation, excitation-contraction coupling, contraction, and relaxation.
• Excitation is the process in which action potentials in the nerve fiber lead to action potentials in the muscle fiber.
• A nerve signal arrives at a synaptic knob, stimulating voltage-regulated Ca2+ gates to open, allowing calcium ions to enter the synaptic knob.
• Ca2+ stimulates exocytosis of synaptic vesicles that release ACh into the synaptic cleft.
• ACh diffuses across the cleft and binds to receptor proteins on the sarcolemma.
• ACh receptors are ligand-gated ion channels and must bind two ACh molecules to open.
• The ligand-gated ion channels then open, Na+ flows in and K+ flows out.
• Then the sarcolemma reverses polarity from -90mV to +75mV, then falls back to close to resting membrane potential as K+ exits.
• The rapid fluctuation in membrane voltage at the motor end plate is called the end-plate potential (EPP).
• Sarcolemma areas adjacent to the NMJ have voltage-gated ion channels that open in response to the EPP, allowing the flow of Na+ in and K+ out, generating an action potential and exciting the muscle fiber.
• Excitation-contraction coupling is the events that link the action potentials on the sarcolemma to activation of the myofilaments.
• A wave of action potentials spreads from the end plate in all directions and enters the T tubules.
• Action potentials open voltage-gated ion channels in the T tubules linked to calcium channels in the terminal cisternae of the sarcoplasmic reticulum (SR).
• When the channels in the SR open, Ca2+ diffuses out of the SR and into the cytosol, down its concentration gradient.
• Calcium then binds to the troponin of the thin filaments.
• The troponin-tropomyosin complex changes shape, exposing the active sites on the actin filaments to make them available for binding to myosin heads.

Contraction

• Contraction is when the muscle fiber develops tension and may shorten, based on the sliding filament theory.
• Myosin ATPase hydrolyzes ATP that is bound to the myosin head into ADP and phosphate (P₁), releasing energy and activating the head, which "cocks" into an extended, high-energy position.
• With ADP and phosphate still bound, the activated myosin head binds to an exposed active site on the thin filament, forming a cross-bridge.
• Myosin releases ADP and P1 and flexes into a bent, low-energy position, which tugs the thin filament along with it (power stroke).
• Upon binding to another ATP, myosin releases the actin, then hydrolyzes the ATP and recocks (recovery stroke). The cycle of power and recovery strokes repeats multiple times and each consumes one molecule of ATP.
• When one myosin releases an actin, many other heads on the same thick filament are still bound to actin on the thin filament so it does not slide back.
• The myofilaments do not become shorter. Instead, the thin filaments slide over the thick ones.
• When nerve stimulation ceases, a muscle fiber relaxes and returns to its resting length.
• Nerve signals stop arriving at the NMJ, so the synaptic knob stops releasing ACh.
• ACh, dissociates from the receptor, breaks down from AChE and reabsorbs but no additional ACh replaces thus broken down.
• The SR simultaneously releases and reabsorbs Ca2+ from excitation through contraction, ceasing Ca2+ release but continues Ca2+ reabsorption.
• Ca2+ in the SR binds to calsequestrin and is stored until stimulation occurs again.
• The level of free calcium in the cytosol decreases since Ca2+ dissociates from troponin and is reabsorbed but not replaced.
• Tropomyosin moves back into position, blocking the active sites of the actin filament and preventing myosin binding.
• A muscle returns to its resting length with the aid of antagonistic muscle contraction and the weight of the body part.
• The amount of tension a muscle generates depends on how stretched or contracted it was before it was stimulated, known as the length-tension relationship
• If a muscle fiber is overly contracted, its thick filaments are very close to the Z discs, unable to contract enough, resulting in a weak contraction.
• If a muscle fiber is overly stretched, there is little overlap between thick/thin filaments, so myosin heads cannot get a grip on the actin, resulting in weak contraction.
• Maximum force generation occurs at an optimum resting length.
• Muscle in its natural position in the living body is never overly stretched or contracted, as the central nervous system continually monitors and adjusts the length of the resting muscle, maintaining muscle tone (a state of partial contraction)

Whole Muscles

• A myogram shows the timing and strength of a muscle's contraction.

Myograms and Muscle Stimulations

• A weak electrical stimulus to a muscle causes no reaction.
• As voltage is increased, the threshold is reached: the action potential causes a reaction.
• At threshold or higher, a stimulus causes a quick cycle of contraction and relaxation called a twitch.
• A delay (latent period) of ~2 milliseconds occurs between stimulus and twitch, and excitation, excitation-contraction coupling, and tensing of elastic components occur.
• Internal tension (force generated) does not show up on the myogram because it causes no shortening of the muscle until elastic components are taut, and the muscle begins to produce external tension and move a resisting object known as the contraction phase of the twitch.
• The contraction phase is short-lived because the SR reabsorbs Ca2+ before the muscle can develop maximum force, so the myosin releases the thin filaments and muscle tension declines -- relaxtion.
• The muscle contracts quicker than it relaxes, so the entire twitch lasts from 7 to 100 ms.
• A subthreshold stimulus induces no muscle contraction, but at threshold, a twitch is produced.
• Increasing the stimulus beyond threshold does not produce stronger twitches.
• Twitch strength depends on how stretched the muscle was just before stimulation, becoming weaker if the muscle become fatigued, warmer muscle contracts stronger than when colder, and the state of hydration of the muscle, which affects the myosin-actin cross-bridge.

Stimulus

• Stimuli arriving close together produce stronger twitches than those arriving far apart
• Stimulus intensity and stimulus frequency have opposite effects.
• At threshold, a weak twitch occurs, and if voltage is increased, twitches are stronger because higher voltages excite more nerve fibers in the motor nerve, stimulating more motor units (recruitment or MMU summation)
• Smaller, slower nerve fibers activate for delicate tasks and larger units activate if more power is needed (size principle)
• At constant voltage, a higher frequency of stimulation produces stronger twitches
• Low frequency stimulation results in an identical twitch for each stimulus and recovers fully
• Higher stimulus frequencies (20 to 40 stimuli/s) results in each new stimulus to arrive before the previous twitch is over and generates higher tension -- temporal summation or wave summation, producing incomplete tetanus.
• Still higher frequencies (40 to 50 stimuli/sec) results in muscle that has no time to relax, fusing a smooth, prolonged contraction (complete tetanus), which is rare because it should not be confused with tetanus caused by the tetanus toxin.
• Contraction does not always mean the shortening of a muscle; contraction can produce internal tension, or no change at all.
• Isotonic contraction is contraction with a change in length but no change in tension.
• Isometric contraction is contraction without a change in length
• Isotonic contraction moves a load as the muscle shortens.
• Both contractions are phases of normal muscular action and have two forms: concentric and eccentric.
• Concentric contraction shortens the muscle as it maintains tension, as when the biceps brachii contracts and flexes the elbow to lift a weight.
• Eccentric contraction lengthens the muscle as it maintains tension, as when the biceps brachii lengthens as a weight is lowered.

Muscle Metabolism

• All muscle contraction depends on ATP.
• ATP supply depends on the availability of oxygen and organic energy sources such as glucose and fatty acids
• Two main pathways of ATP synthesis are anaerobic fermentation and aerobic respiration, used dueing exercise through different mechanisms depending on duration.
• Anaerobic fermentation allows ATP production without oxygen, with the process generating fatigue
• Aerobic respiration produces more ATP and no lactic acid, requiring oxygen
• Resting muscles generate ATP with the fatty acid aerobic respiration, resulting on Oxygen that is stored in myoglobin.
• Muscle borrows phosphate groups from other molecules and transfers them to ADP to form ATP, in which myokinase transfers P from one ADP to another to form ATP or creatine kinase obtains P1 from creatine phosphate (CP) and donates it to ADP to make ATP.
• ATP and CP, collectively the phosphagen system, provide nearly all the energy used for short bursts of intense activity.

Energy and Sustained Activity

• As the phosphagen system exhausts, the muscles shift into anaerobic fermentation for short-term energy unitil the cardipulmonary function catches up with the oxygen demand.
• During this period, muscles obtain glucose from the blood or stored glycogen through the glycogen-lactic acid system, which produces enough ATP for 30 to 40 seconds of maximum activity.
• After 40 seconds, respiratory and cardiovascular systems deliver oxygen to meet most of the ATP demand, resulting with aerobic respiration which produces much more ATP and consuming Oxygen,
• Oxygen consumption rises for 3 to 4 minutes and then levels off at a steady state, in which ATP production keeps pace with demand is reached.
• Muscle fatigue is the progressive weakness and loss of contractility through multiple causes.

Causes of Muscle Fatigue

• Potassium accumulation in the ECF lowers the membrane potential and makes the muscle fiber less excitable
• Accumulation of ADP + P; slows the cross-bridge cycling mechanism of contraction.
• Lactic acid may contribute to fatigue
• Fuel depletion as muscle glycogen and blood glucose declines
• Electrolyte loss through sweating can alter electrolyte balance
• Exercise muscle generate ammonia, which the brain inhibits motor neurons
• VO2max is the point at which the rate of oxygen consumption reaches a plateau, proportional to body size, peaks at around age 20, and is greater in males.
• Excess postexercise oxygen consumption (EPOC), or oxygen debt, is the difference between an elevated rate of oxygen consumption following exercise and the rate of oxygen consumption at rest.
• Excess oxygen consumption is required to aerobically synthesize ATP (regenerate creatine phosphate), reoxygenate myoglobin, oxygen in disposal of lactic acid, exercises and overall metabolic rate that consumes more oxygen.

Muscle Fibers

• Muscle fibers can be separated into physiological characteristics of type I fibers, well adapted endurance, or type IIb fibres adapted for quick movements.
• Slow-twitch fibers, slow fibers resist fatigue due to oxidative metabolism and equipped with dense networks of blood cappilaries abundant mitochondria
• These have sarcoplasmic reticulum that is slow to release or reabsorb calcium, and a form slow in their ATP hydrolysis, with a high myoglobin concentration for a bright red color (red fibers)
• Fast-twitch fibers, have a fast form of calcium release from the sarcoplasmic reticulum and ATP hydrolysis for quick responses, which depends on glycolysis and anaerobic fermentation
• Fiber types and different function: type IIa.
• Every skeletal muscle is composed of slow and fast fibers and these are differ depending on tasks.
• Muscles that mainly compose the first part is called red muscles, the second part is white muscles.
• This proportion differs and depend hereditary.
• Humans have for muscular strength that is not normall, and muscles can generate tension than the bones or the tendon and depend anatomical and physiological factors.
• Some anatomical or physilogical factors are that muscle strength is determined mainly and Pennate are stronger than parallel and circular muscles.
• Large and rested motor units produce strongest contraction and optimum length, and temporal summation of action potentials causes a more stronger contractions.

Exercise and Muscle Growth

• Resistance exercise, like weight lifting, stimulates muscle growth even if limited, primarily through cellular enlargement as myfibils grow thicker and split longitudinally when reaching a certain size.
• Endurance exercise improves fatigue resistance through enhanced oxygen delivery and improves density of blood capillaries.
• Cross-training incorporates elements of both.
• Any types of muscle cells can be called myocytes , term for smooth and cardiac muscle cells (relatively short and have only one nucleus and also called cardiocytes.
• Cardiac and smooth muscle (involontary muscles) are not conscious.
• Cardiac is limited to the hearth where the funtion is to pump

Muscular Requirements

• Cardiac must have to contract with 5 properties of properties of regular rythmnes and resistant fatigue with unisons contaction.
• Each contraction must last long enough to expel blood.
• Cardiac muscle are striated, cardiocytes but the last 4 are shorter and ticker, joined by linkages or desmosomes
• These desmosomes also appears dark section to hold these myocytes together with electrical by electrical communication ( gap junctions) to contract at the same time.
• The sarcoplasmic reticulum of cardiocytes are less development
• Damage causes fibrosis.
• Cardiac contain a built in pacemaker that controls the rythme a wave.
• It is autorhythmic ( controled automatically and independent and it does contain the autonomous system( control and rythmes) but maintain tension in 200 to 250ms.
• Uses aerobic respiration exclusively.

Muscle Type

• Cardiac muscle has rich concentration of mitochondria of 25 % of ATP.
• Is adaptable with respect to fuel, but vulnerable to lack of oxygen, cause less fermentation
• Smooth muscles do not have striations.
• Smooth muscle is NOT innvervation but autonomic.
• The nerve fibers do not form junctions with myocytes.
• Each fiber has is autonomis ( bealike) up to 2000 along length where contrain transmitters.
• Don't motor end pates, the myocites have instead receptors for the transmitters on smooth.
• The smooth do not form organs, ( smaller arteries) variable complexity inn walls
• Is created a fusiform shape in 30 to 200 um long between ( one nucleus only)
• Scanty reticulum don NOT contain T tubules and Z discs contains plagues
• Cytosketal are network and associated densites
• Filament actin with the intermediate is transferred
• The 2 functional ( multion and single unit ) is multiunit, muscles iris are smaller and that the inervation is similar but synaptic with individual myocytes and each myocytes respond independent
• Single unit smooth muscles is more widespread in blood vessels.

Smooth Muscle

• Single unit is the viscera the and the myocytes are electrically coupled the directly together that is call unit electricaly.
• Achieved in with varieties: some fibres innervate automatic.
• These neurotransmitters stimulare smooth with actely and norepilnepe ( oppsite effects in the gastro and dialiating the lungs briones.
• Smooth contract from hormone, oxides.
• Cold smooth temperature areola where warmth relaxes the arteries and stretched contration.
• Some single ( stomach and intestine ) has rhythm.
• Trigger by Ca2 energized by ATP and involves sliding from the
• Most ( NOT FOR ) reticulum
• The chanels have ligand and mechanical
• Smooth has no troponin , then calcium binds to muscle
• Activates a kinase the adds phospate and the that mysin can bind to actin and hydrolyse
• Thick filaments in the densitites the plasma ( shortening entire fibre) and the wrie out and the tension falls slower enzymes
• After as myosin the and attach
• Smooth tetanus but small

Muscle Tone

• Smooth ( faiguye reisstacne and atton)
• Can the toinc can a loss in presure
• The smotth the.
• The
• distesin and with
• Stress stretch the wall and limited also not can and has.
• Zs do the from the and can
• Smotth