Muscle Physiology Notes

Skeletal Muscles

• Generally, both ends of a muscle are attached to bone by tough tendons.

• When a muscle contracts, it shortens.

• This places tension on tendons connecting it to a bone.

• This moves the bone at a joint.

• The bone that moves is attached at the muscle insertion; the bone that does not move is attached at the muscle origin.

• Movement is toward the insertion.

Structure of Skeletal Muscles

• Connective tissue components:

  • Skeletal muscles are surrounded by a fibrous epimysium.

  • Connective tissue called perimysium subdivides the muscle into fascicles.

  • Each fascicle is subdivided into muscle fibers (myofibers) surrounded by endomysium.

Muscle Fiber Structure

• Have many of the organelles found in other cells.

• Have plasma membranes called sarcolemma.

• Are multinucleated.

• Are striated:

  • I bands: light bands

  • A bands: dark bands

  • Z-lines (discs): dark lines in the middle of the I bands

Motor Units

• A motor unit is a single motor neuron and all the muscle fibers it innervates; all the muscle fibers in a motor unit contract at once.

• Graded contractions – varied contraction strength due to different numbers of motor units being stimulated (at varying frequencies).

• Neuromuscular junction: site where a motor neuron stimulates a muscle fiber.

• Motor end plate: area of the muscle fiber sarcolemma where a motor neuron stimulates it using the neurotransmitter, acetylcholine.

• Control of motor units:

  • Contraction force comes from motor unit recruitment and frequency of recruitment.

  • Finer muscle control requires smaller motor units (fewer muscle fibers).

    • The eye muscles may have ~23 muscle fibers/motor units.

    • Larger, stronger muscles may have motor units with thousands of muscle fibers.

    • Control and force are trade-offs.

Mechanisms of Contraction

• Each muscle fiber has densely packed subunits called myofibrils that run the length of the muscle fiber.

• Composed of thick and thin myofilaments.

• Striations:

  • Produced by thick and thin filaments

    • I bands contain only thin filaments, composed primarily of the protein, actin.

    • A bands contain all of the thick filament with some thin filament overlap; the thick filament is the protein, myosin.

    • H zone/band are the center of the A band with no thin filament overlap.

    • Z discs (lines) are found in the center of each I band.

The Sarcomere

• The functional unit of striated muscle contraction.

• Area from one Z disc to the next.

• Titin: protein that runs from the Z disc to the M line and allows elastic recoil (and possibly aids eccentric contractions).

• M lines are found in the center of each A band and help hold down thick filaments.

• In three dimensions, the sarcomere forms a hexagonal pattern.

Sliding Filament Theory

• When a muscle contracts, sarcomeres shorten:

  • A bands do not shorten, but move closer together.

  • I bands do shorten, but thin filaments do not.

  • Thin filaments slide toward the H zone.

  • H zone shortens or disappears.

Cross Bridges

• Myofilaments:

  • Thick: composed of the protein myosin

    • Each protein has two globular heads with actin-binding sites and ATP-binding sites.

  • Thin: composed of the protein actin

    • Have regulatory proteins called tropomyosin and troponin that prevent myosin binding at rest.

  • Action of sliding:

    • Sliding is produced by several cross bridges that form between myosin and actin.

    • The myosin head serves as a myosin ATPase enzyme, splitting ATP into ADP + Pi.

    • This allows the head to bind to actin when the muscle is stimulated.

      • Myosin head can bind to either ATP OR actin, but not both simultaneously

    • Release of Pi upon binding, produces a power stroke that pulls the thin filament toward the center.

      • Sequence of ‘attach, pivot, detach, return’

    • After the power stroke, ADP is released and a new ATP binds.

      • This makes myosin release actin.

      • ATP is split once again by myosin ATPase.

      • The myosin head straightens out and rebinds to actin farther back.

    • Continues until the sarcomere has shortened.

Regulation of Contraction

• F-actin (Filamentous) is made of 300-400 G-actin (Globular) subunits, arranged in a double row and twisted to form a helix.

• Tropomyosin physically blocks cross bridges.

• Troponin complex:

  • Troponin I inhibits binding of myosin (binds to actin).

  • Troponin T binds to tropomyosin.

  • Troponin C binds to calcium.

• Role of Calcium:

  • When muscle cells are stimulated, Ca^{2+} is released inside the muscle fiber.

  • Attaches to troponin C, causing a conformational change in troponin and tropomyosin.

  • Myosin is allowed access to form cross bridges with actin.

Excitation-Contraction Coupling

• Sarcoplasmic reticulum (SR):

  • SR is modified endoplasmic reticulum that stores Ca^{2+} when muscle is at rest.

  • Most is stored in terminal cisternae.

  • When a muscle fiber is stimulated, Ca^{2+} diffuses out of calcium release channels (ryanodine receptors).

  • At the end of a contraction, Ca^{2+} is actively pumped back into the SR (Ca^{2+} - ATPase pump).

• Transverse Tubules (T-Tubules):

  • Narrow membranous tunnels formed from the sarcolemma.

  • Open to the extracellular environment.

  • Able to conduct action potentials.

  • Closely situated next to terminal cisternae (form triads with 2 terminal cisternae on either side and t-tubule in center).

• Stimulating a Muscle Fiber:

  • Acetylcholine is released from the motor neuron.

  • End plate potentials are produced.

  • Action potentials are generated (All-or-none event).

  • Voltage-gated channels (DHP channels) in transverse tubules change shape and cause opening of calcium channels in SR (Ryanodine Receptors) to open.

  • Calcium is released and binds to troponin C.

  • The troponin complex rolls tropomyosin away, exposing myosin binding sites on the actin filament.

  • Myosin heads can now bind actin and undergo powerstroke.

Muscle Relaxation

• Action potentials cease.

• Calcium release channels close.

• Ca^{2+}-ATPase pumps move Ca^{2+} back into SR (active transport).

• No more Ca^{2+} is available to bind to troponin C.

• Tropomyosin moves to block the myosin heads from binding to actin.

Contractions of Skeletal Muscles

• Electrical stimulations are applied to muscle (in laboratory setting), and contractions are recorded and displayed as currents.

• Twitch, Summation, and Tetanus:

  • Twitch: when a muscle quickly contracts and relaxes after a single electrical shock of sufficient voltage

    • Increasing the voltage increases the strength of the twitch up to a maximum.

    • When a second shock is applied immediately after the first, a second twitch will partially piggyback the first. This is called summation.

    • Latent period – time between the stimulus and the contraction (excitation-contraction coupling to the attachment of myosin cross bridges to actin).

    • Graded contractions – stronger contractions result in recruitment of more fibers, until all fibers are contracting.

  • Tetanus:

    • Increasing the frequency of electrical shocks decreases the relaxation time between twitches. This is called incomplete tetanus.

    • At a certain frequency, there will be no relaxation. This is called complete tetanus, a smooth, sustained contraction.

    • Tetanus In Vivo (= in living organism)

      • Asynchronous activation of motor units.

      • Some motor units start to twitch when others start to relax.

      • This produces continuous contraction of the whole muscle.

      • Recruitment makes contractions stronger.

  • Treppe

    • As the voltage is increased, the number of muscle fibers used in vitro increases.

    • This will reach a maximum value when all muscle fibers are stimulated.

    • If a fresh muscle is stimulated with several shocks at maximum voltage, each twitch will be progressively stronger.

    • When recorded, this will produce a staircase effect called treppe.

Types of muscle contractions and factors affecting tension:

• Force Velocity Curve

  • For muscles to contract, they must generate force that is greater than the opposing forces.

  • The greater the force, the slower the contraction.

• Isotonic Contractions

  • Isotonic contraction: Muscle fibers shorten when the tension produced is just greater than the load.

    • Concentric contraction: A muscle fiber shortens when force is greater than load.

    • Eccentric contraction: A muscle may actually lengthen, despite contraction, if the load is too great.

    • Allows you to lower a weight gently after a full concentric contraction

• Isometric contraction

  • Muscles can’t shorten because the load is too great.

  • Can be voluntary

• Length-Tension Relationship

  • Muscle strength is determined by:

    • Number of fibers recruited to contract

    • Frequency of stimulation

    • Cross-sectional area (CSA) of each muscle fiber (thicker is stronger)

    • Initial length of the fiber at rest = Length-Tension Relationship

      • Tension is maximal when sarcomeres are at normal resting length.

      • Increasing sarcomere length decreases muscle tension.

      • There are fewer interactions between myosin and actin.

      • At a certain point, no tension can be generated.

      • Decreasing sarcomere length decreases muscle tension because the fiber gets shorter and thicker

      • Increased fluid pressure

      • Increased distance between the actin and myosin

Energy needed for

• Myosin ATPase (70%)

• Ca^{2+} pump to actively return calcium to the SR (30%)

• Where Muscles Get Their Energy:

  • At rest and for mild exercise: from the aerobic respiration of fatty acids

  • For moderate exercise: from glycogen stores

  • For heavy exercise: from blood glucose, free ATP, PC System

  • As exercise intensity and duration increase, GLUT4 channels are inserted into the sarcolemma to allow more glucose into cells.

Metabolism of Skeletal Muscle

• Anaerobic for the first 45-90 seconds of moderate to heavy exercise

• Allows time to increase oxygen supply

• Maximal Oxygen Uptake

  • Also called aerobic capacity, or VO2 max

  • Determines whether a given exercise is light, moderate, or heavy for a given person

  • Determined by a person’s age, sex, size, and athletic training

  • Greater for males and younger people

  • Ranges from 12 ml O2/minute/kg body weight to 84 ml O2/minute/kg body weight

• Lactate Threshold (LT)

  • Also called anaerobic threshold (AT)

  • % of maximal oxygen uptake at which a rise in blood lactate levels occurs

  • Occurs at about 50−70% VO2 max

  • Need for glucose increases during exercise

  • More GLUT4 receptors in plasma membrane

  • Blood glucose levels drop, blood lactate concentration increases

  • Liver provides more glucose through hydrolysis of glycogen and through gluconeogenesis.

• Oxygen Debt (Excess Post-Exercise Oxygen Consumption, EPOC)

  • When a person exercises, oxygen is withdrawn from reserves in hemoglobin and myoglobin.

  • To create cross bridges in muscle contraction and pump calcium back into SR at rest

  • To metabolize lactic acid

  • Breathing rate continues to be elevated after exercise to repay this debt.

• Phosphocreatine System

  • ATP may be used faster than it can be created through cellular respiration.

  • ADP is combined with Pi from phosphocreatine.

  • Creatine is produced by the liver and kidneys or obtained in the diet.

  • Phosphocreatine stores are replenished at rest.

  • Creatine supplements can increase muscle phosphocreatine and aid short-term high-energy exercise, but long-term use may have negative effects.

Slow- and Fast-Twitch Fibers

• Slow-twitch (type I): slower contraction speed; can sustain contraction for long periods without fatigue; rich capillary supply; more mitochondria; more respiratory enzymes; more myoglobin

  • Said to have high oxidative capacity, so are called slow oxidative fibers (SO)

  • Due to high myoglobin content (which has a red pigment), these are also called red fibers

  • Found in postural muscles

• Fast (type IIx/b): faster contraction speed, fatigue fast, fewer capillaries, mitochondria, respiratory enzymes, and less myoglobin

  • Also called white fibers

  • Have more glycogen stores and are called fast glycolytic fibers (FG)

  • Found in larger/more powerful muscles

• Intermediate (type IIA): fast-twitch but with high oxidative capacity; called fast oxidative/glycolytic fibers (FOG)

• People vary greatly in the percentage of fast- or slow-twitch fibers in their muscles; result of genetics and training

• Characteristics:

  • Fast Twitch:

    • Velocity of contraction: Fast

    • Diameter: Large

    • Pathway to regenerate ATP: Anaerobic (PC system, glycolysis)

    • Amount of stored glycogen: High

    • Fatigue resistance: Low

    • Force: High

    • Motor unit size: Large

    • Mitochondria/Myoglobin: Low

  • Slow Twitch:

    • Velocity of contraction: Slow

    • Diameter: Small

    • Pathway to regenerate ATP: Aerobic

    • Amount of stored glycogen: Low

    • Fatigue resistance: High

    • Force: Low

    • Motor unit size: Small

    • Mitochondria/Myoglobin: High

Muscle Fatigue

• Reduced ability to generate force

• Due to:

  • Accumulation of extracellular K^+, reducing membrane potential

    • Short duration – can return to normal after short rest

  • Depletion of stored glycogen

  • Reduced SR calcium release

  • Lactic acid accumulation and lower pH

  • Increased concentration of PO_4 due to phosphocreatine breakdown

  • Lack of ATP

  • Buildup of ADP

  • Fatigue of upper motor neurons (in the CNS), called central fatigue

Muscle Damage and Repair

• Skeletal muscles have stem cells called satellite cells located near muscle fibers.

• These can fuse to damaged muscle cells and repair them or fuse to each other to form new muscle fibers.

• Myostatin is a paracrine regulator that inhibits satellite cells.

Adaptations to Endurance Exercise Training

• Increased ability to use fatty acids as fuel and increased intracellular triglyceride storage

• Increased lactate threshold

• Decrease in type IIx and increase in type IIA muscle fibers

• Decreased insulin sensitivity

• Increase in number of mitochondria

Adaptation to Strength Training

• Hypertrophy: Type II muscle fibers become thicker due to increased amount of actin and myosin (more sarcomeres).

• Thicker myofibrils can split into two myofibrils, which can also increase in size.

Muscle Decline with Aging

• Reduced muscle mass (usually type II fibers)

  • Can be reduced with strength training

• Reduction in capillary blood supply

  • Can be reduced with endurance training

• Fewer satellite cells, increased myostatin production

Muscle Sensory Organs

• Muscles are made of thin muscle cells called intrafusal fibers and regular muscle fibers called extrafusal fibers

• Golgi tendon organs: respond to tension a muscle puts on a tendon

• Muscle spindle apparatus: respond to rapid changes in muscle length

  • Muscles that require more control have more spindles.

  • Rapidly stretching a muscle causes spindles to stretch.

  • Muscle spindle apparatus contains thin muscle cells called intrafusal fibers

  • Two types of intrafusal fibers:

    • Nuclear bag fibers – nuclei in loose central aggregates (‘bag’)

    • Nuclear chain fibers – nuclei in rows (‘chain’)

  • Two types of sensory cells wrap around the fibers:

    • Primary (annulospiral) – most stimulated at the beginning of the stretch

    • Secondary (flower-spray) – respond more during sustained stretch

• Alpha and Gamma Motoneurons

  • Alpha: innervate extrafusal (contracting) muscle fibers

  • Gamma: innervate intrafusal (active stretch) muscle fibers

    • Contraction of these fibers does not shorten the muscle, but does increase sensitivity to stretch.

    • Provides enough tension during relaxation to maintain muscle tone

  • Both types are stimulated by upper motor neurons at the same time - coactivation

Skeletal Muscle Reflexes

• Skeletal muscles are usually referred to as voluntary and are controlled by descending motor pathways under conscious control

• They can also contract unconsciously in response to certain stimuli – a reflex

• Monosynaptic Stretch Reflex

  • Simplest reflex

  • Only involves a sensory neuron synapsing on a motor neuron in the spinal cord

  • One synapse – monosynaptic

  • Maintains optimal resting length of skeletal muscles – muscle stretch reflex

  • Can be stimulated by striking the patellar ligament in the “knee-jerk reflex”

• Golgi Tendon Organs

  • Constantly monitor tension in tendons

  • Sensory neuron stimulates interneuron in spinal cord.

  • Interneuron inhibits motor neuron.

  • Tension in tendon is reduced.

  • Disynaptic reflex involving two synapses

• Reciprocal Innervation

  • In the knee-jerk reflex, interneurons are also stimulated in the spinal cord to inhibit antagonistic muscles on that limb.

  • More complex reflexes require control of muscles on the contralateral limb. This is called double reciprocal innervation.

• Crossed Extensor Reflex

  • Type of double reciprocal innervation seen when you step on a tack

Cardiac and Smooth Muscles

• Cardiac and smooth muscles are:

  • Involuntary

  • Regulated by autonomic nervous system

  • Like skeletal muscle, contraction is due to myosin/actin cross bridges stimulated by calcium

• Cardiac Muscle

  • Striated

  • Myosin and actin filaments form sarcomeres.

  • Contraction occurs by means of sliding thin filaments.

  • Unlike skeletal muscle fibers, these fibers are short, branched, and connected via gap junctions called intercalated discs (electrical synapses that permit impulses to be conducted cell to cell).

• Myocardium

  • A myocardium is a mass of cardiac muscle cells connected to each other via gap junctions.

  • Action potentials that occur at any cell in a myocardium can stimulate all the cells in the myocardium.

  • It behaves as a single functional unit/syncytium

  • The atria of the heart compose one myocardium, and the ventricles of the heart compose another myocardium.

• Pacemaker Potential

  • Cardiac muscle can produce action potentials automatically (without innervation).

  • Begin in a region called the pacemaker

  • Heart rate is influenced by autonomic innervation and hormones.

  • Calcium Channels

    • Unlike skeletal muscle, the voltage-gated calcium channels are not directly connected to calcium channels in the SR.

    • Instead, calcium acts as a second messenger to open SR channels.

    • Called calcium-induced calcium release

    • Excitation-contraction coupling is slower.

• Smooth Muscle

  • Found in blood vessel walls, bronchioles, digestive organs, urinary and reproductive tracts

  • Produce peristaltic waves to propel contents of these organs

  • No sarcomeres, but still contain large amounts of actin and myosin

  • Long actin filaments attached to dense bodies

  • Myosin filaments are stacked vertically and can form cross bridges with actin its entire length

  • Arrangement allows contraction even when greatly stretched

• Single-unit and Multi-unit Smooth Muscles

  • Single-unit: multiple gap junctions that make neighboring cells behave as a unit

    • Most smooth muscles are single-unit.

    • They display pacemaker activity moderated by stretch or autonomic innervation.

    • Only a few cells in a single-unit receive acetylcholine stimulation.

    • Muscarinic ACh receptors respond by closing K^+ channels.

  • Multi-unit: require individual nerve innervation (no pacemaker activity)

    • Few or no gap junctions

    • Arrector pili muscles in skin and ciliary muscles in eyes are multi-unit