Muscle Tissue: Types and Function

Introduction

• Muscle cells are specialized to produce force and do work
• Muscle cells utilize a highly developed microfilament system
• Muscle cells can shorten and develop tension
• Muscle cells convert chemical energy of ATP into mechanical energy that can act on the environment
• The 3 types of muscle cells are skeletal, cardiac, and smooth
• Muscle contraction permits purposeful locomotory movement
• Muscle contraction enables manipulation of external objects
• Muscle contraction facilitates propulsion of contents through hollow internal organs
• Muscle contraction aids in emptying the contents of certain organs into the external environment
• Muscle contraction facilitates the production of heat
• Muscle contraction enables the production of sound

Skeletal Muscle

• Skeletal muscle makes up the muscular system
• Skeletal muscle cells (muscle fibers) are large, ranging from 10-100µm in diameter, elongated, and cylindrical in shape
• Skeletal muscle cells are formed by the fusion of many myoblasts during embryonic development, resulting in multiple nuclei
• Skeletal muscle cells lie parallel to each other and are bundled together by connective tissue
• Skeletal muscle cells extend the full length of the muscle
• Damaged or destroyed muscle fibers undergo repair by undifferentiated stem cells (satellite cells) after birth

Myofibrils

• Myofibrils are specialized contractile elements
• Myofibrils typically make up 90% of muscle volume
• Myofibrils are cylindrical intracellular organelles that extend the entire length of the muscle fiber
• The greater the density of myofibrils, the greater the force that can be generated
• Muscle fibers with a low percentage of myofibrils cannot generate much tension but can contract at a high frequency
• Myofibrils show a regular arrangement of thick and thin filaments
• Thick filaments measure 12-18 nm in diameter and 1.6µm in length
• Thick filaments are composed of the contractile protein, myosin
• Tails of thick filaments are intertwined with globular heads projecting out at one end
• Each globular head of a thick filament has an actin binding site and an ATPase
• Thin filaments are 5-8 nm in diameter and 1.0µm in length
• Thin filaments are composed of the contractile protein, actin
• Thin filaments have sites for attachment to myosin
• Tropomyosin forms strands that cover actin binding sites when muscle is relaxed
• Troponin is a protein complex with three subunits: one binds tropomyosin, one binds actin, and one can bind with Ca2+
• When not bound to Ca2+, troponin stabilizes tropomyosin in its blocking position

Skeletal Muscle Striations

• Skeletal muscle striations show alternating dark bands (A bands) and light bands (I bands)
• The A band consists of a stacked set of thick filaments and portions of thin filaments that overlap them
• The H zone is the lighter area in the middle of the A band, where only thick filaments are present without overlapping thin filaments
• The M line located in the center of the A band, holds thick filaments together
• The I band consists of thin filaments where they do not overlap with thick filaments
• The Z line is in the center of the I band, a flat cytoskeletal disc where thin filaments connect
• The sarcomere is the area between two Z lines
• The Sarcomere is the functional unit of skeletal muscle and measures 2.5µm in width

Sliding Filament Theory

• During contraction, thin filaments slide toward the center of the A band, resulting in shortening of the sarcomere
• Neither thick nor thin filaments change length

Molecular Basis of Contraction

• Cross-bridge cycling occurs during muscle contraction
• Ca2+ binds to troponin, changing its shape and uncovering the binding sites on actin
• Myosin globular heads (cross-bridges) bind to actin
• The cross-bridge bends 45° inward, pulling the thin filament with it (power stroke)
• Myosin detaches from actin and returns to its original conformation, attaching to a new site on actin
• Complete shortening is accomplished by repeated cross-bridge cycles
• Myosin ATPase on thick filaments splits ATP to form adenosine diphosphate (ADP) and inorganic phosphate (Pi)
• ADP and Pi remain attached to myosin, energizing it
• During and after the subsequent power stroke, Pi and ADP are released
• Myosin ATPase site attaches a new ATP molecule
• Attachment of new ATP permits detachment of the cross-bridge, setting up for another power stroke

Neuromuscular Junction

• The terminal button (aka boutons) of the axon terminal fits into a shallow depression in the muscle cell membrane, called the motor end plate
• Acetylcholine (ACh) is stored in synaptic vesicles in the presynaptic terminal
• Each muscle fiber is innervated by only one motor neuron, but one motor neuron innervates multiple muscle fibers

Neuromuscular Transmission

• Neuromuscular transmission occurs in the following steps:
  • Presynaptic: An action potential reaches the axon terminal, opening voltage-gated Ca++ channels, allowing Ca++ to enter
  • ACh is released by exocytosis
  • Postsynaptic: ACh binds to cholinergic receptors, opening chemically-gated nicotinic ion channels in the motor end plate, leading to graded depolarization (end plate potential, EPP)
  • This initiates an action potential, which spreads throughout the muscle cell membrane by continuous conduction
  • The action potential initiates contraction of the muscle fiber
• An EPP in a muscle fiber is much larger than an EPSP in a neuron because:
  • There are multiple terminal buttons in the neuromuscular junction
  • More neurotransmitter molecules are released at each terminal button
  • The motor end plate has a larger surface area with a higher density of receptors
  • This produces more receptor-channels
  • A single EPP is sufficient to initiate an action potential
• ACh binding is reversible and can be terminated
  • ACh binds briefly to cholinergic receptors, then detaches
  • ACh is inactivated by acetylcholinesterase, an enzyme located in the motor end plate
  • Removal of ACh terminates the EPP

Molecular Basis of Skeletal Muscle Contraction

• Ca2+ is the link between excitation and contraction
• Skeletal muscles are stimulated to contract by the release of acetylcholine (ACh) at neuromuscular junctions, causing an EPP
• The resulting action potential is conducted along the muscle cell membrane
• The surface membrane dips deeply into the muscle fiber to form a transverse tubule (T-tubule)
• The action potential enters the interior of the muscle fiber along the T-tubules
• This process induces permeability changes in the adjacent sarcoplasmic reticulum
• Ca2+ is stored in the lateral sacs of the sarcoplasmic reticulum (SR), where Ca2+-binding protein calsequestrin stores a large quantity of Ca2+
• As an action potential enters the interior of the muscle fiber along the T-tubules, it causes a conformational change in the Dihydropyridine (DHP) receptor, which acts as a voltage sensor and slowly activating calcium channel
• DHP interacts with the Ryanodine receptor (RyR) to trigger Ca2+ release from the SR
• Elevated cytosolic Ca2+ results in increased binding of Ca2+ to troponin, initiating contraction
• During relaxation, Ca2+ is pumped back into the sarcoplasmic reticulum by Ca2+-ATPase pumps, reducing cytosolic Ca2+ levels

Muscle Fiber Action Potential

• Contractile activity outlasts the action potential that created it
• A single action potential lasts 1-2 msec
• A single action potential in a muscle fiber produces an all-or-none muscle contraction (twitch) after a short latent period
• The latent period is the time after the AP, but before tension in the muscle fiber begins to increase
• Contraction time is the interval from beginning tension development at the end of the latent period to peak tension (averages 50 msec)
• Contraction continues until the completion of Ca2+ release
• Relaxation time is slightly longer and occurs as Ca2+ is pumped back into the SR
• Total twitch time is about 100 msec
• There are fast-twitch fibers and slow-twitch fibers
• A single action potential in a muscle fiber produces an all-or-none contraction
• Each vertebrate muscle fiber is supplied by only one motor neuron
• Each motor neuron branches and innervates many muscle fibers
• All the muscle fibers innervated by one motor neuron will contract simultaneously, forming a motor unit

Motor Units

• More motor units are stimulated to contract to produce stronger muscle contractions (motor unit recruitment)
• Muscles that provide precise, delicate movements have few muscle fibers per motor unit (e.g., external eye muscles)
• Muscles used for powerful, coarsely controlled movement have many muscle fibers per motor unit (e.g., leg muscles)
• Asynchronous recruitment of motor units is coordinated by the brain to prevent fatigue
• Every muscle has an optimal length (lo) at which maximal force can be achieved upon tetanic contraction

Length-Tension Relationship

• A muscle’s sliding-filament Mechanism explains its length-tension relationship
• Maximum tension is achieved when the maximal number of cross-bridge sites are accessible to actin for binding
• Muscles are usually stretched to their l0 by normal attachment to the skeleton

Load-Velocity Relationship

• The greater the load, the lower the velocity of shortening
• Velocity falls to zero when the load exceeds tension (isometric contraction)

Repetitive Stimulation of Muscle Fibers

• If a muscle fiber is stimulated before it relaxes from a previous stimulus, the second contraction is added to the first (twitch summation)
• This happens because the duration of the muscle contraction is much longer than the duration of the action potential
• Factors contributing to twitch summation include sustained elevation of cytosolic Ca2+
• If a muscle fiber is stimulated so rapidly that it has no chance to relax at all between stimuli, a smooth sustained contraction occurs (tetanus)
• Graded muscle contractions are produced by controlling the number of motor units stimulated and the frequency of their stimulation
• Tetanic contractions and asynchronous motor unit recruitment are used in normal physiological motor control

Skeletal Muscle Mechanics

• For a muscle to shorten during contraction, the tension must exceed the forces that oppose movement (load)
• Isotonic contraction:
  • Muscle shortens
  • Muscle tension remains constant
  • Work is done (work = force x distance)
• Isometric contraction:
  • Muscle is prevented from shortening
  • Tension develops at constant muscle length
  • No work is done
• Concentric contraction: Tension exceeds the load, shortening occurs
• Eccentric contraction: Muscle lengthens during contraction because it is being stretched by an external force