Muscle Physiology

Skeletal Muscle

• Striated 

• Attached to bones (voluntary movement, posture, and stabilization) 

• Innervated by somatic motor neurons that stimulates contractions 

Cardiac Muscle

• Striated 

• Heart (pumps blood) 

• Does not require nervous stimulation to contract (autorhythmic) 

Smooth Muscle

• Non-striated

• Found in walls of visceral organs and blood vessels 

• Not subject to voluntary control 

Electrical excitability

In response to AP, muscle contracts (excitation-contraction coupling)

Contractility 

• Ability to generate tension/force in response to AP; if tension generated is greater than load placed on muscle, movement occurs 

Extensibility

Ability of muscle to be stretched without damage

Elasticity 

Ability to return to original shape and length after extension 

Structure of skeletal muscle

• Encased by connective tissue (epimysium) 

• Comprised of bundles of fascicles 

  • Each fascicle = bundles of muscle fibers

Muscle (organ)

consists of hundreds to thousands of muscle cells, plus connective tissue wrappings, blood vessels, and nerve fibers 

What are its connective tissue wrappings/what surrounds it? 

Covered externally by epimysium 

Fascicle (a portion of the muscle)

a discrete bundle of muscle cells segregated from the rest of the muscle by a connective tissue sheath 

What are its connective tissue wrappings/what surrounds it? 

surrounded by perimysium 

Muscle fiber (cell)

an elongated multinucleate cell (has banded/striated appearance)

What are its connective tissue wrappings/what surrounds it? 

surrounded by endomysium 

Myofibril/fibril (complex organelle composed of bundles of myofilaments) 

rodlike contractile elements that occupy most of the muscle cell volume; made of chains of sarcomeres

composed of sarcomere arranged end to end (appears banded) and bands of adjacent myofibrils are aligned 

singular muscle cell = muscle fiber

• Sarcolemma = cell membrane 

• Sarcoplasm = cytoplasm 

• Multinucleate = many nuclei per fiber 

• Sarcoplasmic reticulum = modified smooth ER: stores Ca2+ 

• Myoglobin = red pigments similar to hemoglobin 

  • Contains Fe2+ that binds O2 = O2 reservoir 

• Myofibrils = bundles of contractile and elastic proteins that run length of muscle fibers (80% of volume of muscle) 

Sarcomeres

• Units of contraction in skeletal and cardiac muscle 

• Made of proteins 

• “Thick” filaments = myosin (myosin proteins form thick filaments)

• “Thin” filaments = actin (actin proteins form thin filaments) 

• Creates “striated” appearance 

Regions of sarcomere

• I-band

• Z-disk 

• A-band 

• H-zone 

• M-line 

Z-disk 

• Dark area in middle of I-band 

• appears light under microscope

• anchors thin filaments; marks boundary between adjacent sarcomeres 

• when muscle contracts, Z-disks move closer together, shortening sarcomere 

I-band (Isotropic = light)

• region occupied by thin filaments only

• appears light under microscope

• I-band shortens as thin filaments slide in

A-band (Anisotropic = dark)

• Dark-colored band under microscope 

• runs entire length of thick filaments 

• A-band stays the same length during contraction as length of thick filaments don’t change during contraction 

H-zone

• Located in middle of A-band, where thick filaments are present but no overlap with thin filaments 

• only thick filaments (no actin) 

• visible in relaxed fibers only; gets smaller/disappears in contraction 

M-line

• Dark line in middle of A-band (middle of H-zone/center of sarcomere) 

• seen as the “anchor point” for myosin proteins 

• holds thick filaments in place and aligns them 

Myofilaments 

“actual” contractile threads that slide past each other to allow contraction to occur

made up of two types:

• thin filaments 

  • actin 

  • tropomyosin 

  • troponin 

• thick filaments 

  • myosin 

Actin (thin filament)

• Globular protein molecules (G actin) 

• Each G actin molecule has binding site for myosin (thick filament) 

• along actin filament contains: 

  • tropomyosin (covers binding sites when muscle is relaxed)

  • troponin (binds calcium & moves tropomyosin out of the way when contraction happens) 

Tropomyosin (2 strands)

• Elongated protein that spirals around actin strands 

• In relaxed muscle, blocks myosin binding site on actin 

Troponin (thin filament)

• Attached to tropomyosin 

• has binding sites for Ca2+ 

  • When calcium is bound, troponin and tropomyosin move out of the way to expose myosin binding site on actin

Myosin (thick filament)

• Motor protein that pulls on actin to make muscle contract 

• Contains: 

  • Myosin tails 

    • Pointed toward each other 

  • Myosin heads 

    • Pointed away from one another 

    • Can move at point of attachment to tail 

    • Two binding sites 

      • For ATP (part of myosin is ATPase) 

      • For actin

Sliding filament theory

• Muscle contraction occurs when thin filaments (actin) slides over thick filaments (myosin), shortening sarcomere (filaments do not change length however) 

• myosin heads pull on thin filaments, causing them to slide inward toward M-line 

Sarcoplasmic Reticulum (SR)

• modified version of smooth ER found in muscle cells 

• system of tubules that stores/releases Ca2+ ions 

• surrounds each myofibril 

• at rest, stores Ca2+ ions in terminal cisternae 

• during contraction, releases Ca2+ ions into sarcoplasm 

• during relaxation, reabsorbs Ca2+ to stop contraction

Terminal cisternae

Enlarged areas of SR adjacent to t-tubules that help with the storage of Ca2+ ions at rest and the release of Ca2+ ions during contraction 

Triads 

Specialized junction formed by T-tubules that aids in excitation-contraction coupling

• helps transmit nerve signal deep into muscle fiber 

• when signal reaches t-tubule, triggers terminal cisternae to release Ca2+ ions 

• consists of: 

  • a t-tubule 

  • two terminal cisternae 

Transverse tubules (t-tubules) 

• Channels that are continuous with extracellular space; inversions of sarcolemma 

• Penetrates deep into cell; runs between terminal cisterns, encircles each myofibril 

• Function: 

  • Conducts AP to every sarcomere, including those in center of muscle fiber

Two forms of myosin heads? 

• low energy form 

• high energy form

Cross-bridge cycling

• repeated attachment, “pivot”, and detachment of myosin heads on actin filaments that shorten sarcomeres during muscle contractions 

• 1 ATP consumed per cycle 

• Ca2+ released from SR and binds troponin 

• Several binding/unbinding cycles for single contractions 

• Cross-bridges work independently and asynchronous 

Cross-bridge formation 

• post-actin sites being exposed for myosin to attach

• energized myosin head attaches to an actin myofilament, forming a cross bridge 

Power/working stroke

• ADP and phosphate are released and the myosin pivots and bends, changing to it’s low-energy state, pulling the actin filament toward M-line 

  • In absence of ATP, myosin head will not detach, causing rigor mortis 

Cross-bridge detachment

• After ATP attaches to myosin, link between myosin and actin weakens, making the myosin head detach/cross bridge “breaks” 

Cocking of the myosin head

As ATP is hydrolyzed to ADP and phosphate, myosin head returns to high-energy/”cocked” position and cycle can continue

Rigor mortis

• stiffness/rigidity of muscle postmortem (after death) 

• Cells die, membranes lose integrity, Ca2+ leaks in, causing cross-bridge formation 

• Actin and myosin can’t detach from one another as body has run out of ATP, therefore actin cannot “unlock” myosin and, as a result, great muscle stiffness occurs 

Role of calcium

• Relaxed muscle cross-bridges are “primed” (ADP + P) but are unable to generate power stroke 

  • Ca2+ from sarcoplasmic reticulum is required to expose myosin binding sites on actin via troponin/tropomyosin complex 

• An AP must be generated and travel alongside the sarcolemma and into t-tubules (excitation-contraction coupling) 

Excitation-Contraction Coupling

• “Series of events that link muscle excitation from a nerve impulse into contraction”

• Nerve signal to Ca2+ release to muscle contraction (in short) 

Excitation-Contraction Coupling Step 1

action potential from presynaptic motor neuron triggers exocytosis of ACh

at neuromuscular junction, acetylcholine is released 

(

Excitation-Contraction Coupling Step 2 

ACh binds to ligand-gated channels on sarcolemma and causes a net inward movement of Na+, initiating an muscular action potential 

Excitation-Contraction Coupling Step 3

Action potential propagates over cell membrane and depolarizes t-tubules, triggering terminal cisternae of SR/sarcoplasmic reticulum to release Ca2+ into sarcoplasm 

Excitation-Contraction Coupling Step 4 

• Ca2+ ions bind to troponin and tropomyosin, exposing myosin-binding sites on actin 

• Cross-bridge cycling occurs as long as Ca2+ remains bound to troponin

  • myosin heads attach to actin, sliding filament cycling 

  • myosin pulls actin toward M-line, shortening sarcomere and contracting muscle 

Excitation-Contraction Coupling (Relaxation)

• Ca2+ ions are pumped back into SR

• tropomyosin covers actin binding sites, detaching myosin (muscle relaxes) 

• AChE (acetylcholinesterase) ensures sarcolemma isn’t stimulated by breaking down remaining ACh in synaptic cleft

Neural Control

• Each somatic motor neuron branches to innervate two or more skeletal muscle fibers 

• Each fiber receives input from only one motor neuron (even if motor neuron innervates multiple fibers) 

• Each motor unit can tell any number of muscle fibers to contract (as long as it innervates multiple)

Muscles which control precise movements tend to have? 

Many small motor units 

• EX: larynx/hand muscles: 2-3 muscle fibers per motor unit 

• EX: muscles which move eyes: ~10-20 fibers per unit 

Muscles which control larger powerful movements tend to have?

Larger motor units

• EX: gastrocnemius of calf/biceps in arms: 2000 fibers per unit

Fibers in a motor unit are spread throughout muscle, so when one motor unit is stimulated, the result is? 

A weak contraction of entire muscle (twitch) 

• structure is designed to allow whole muscle to contract as a “designated unit” 

Motor unit 

Somatic motor neuron with the fibers it innervates 

Muscle twitch

• Response of a motor unit to a single AP in its motor neuron

• usually only observed experimentally

How can muscles generate different amounts of tension depending on the load? 

• Increasing the number of fibers/motor units participating in the contraction (motor unit recruitment) (response of a muscle to increased stimulus strength) 

• Increasing the tension developed by each contracting fiber (twitch/wave summation and tetanus) (response of muscle fiber to increased frequency of stimulation) 

Motor Unit Recruitment 

• Process of increasing the # of motor units involved in the contraction (Controlled by CNS) 

• As the load placed on a muscle increases, muscles respond in the following way: 

  • The number of somatic motor neurons firing increases which then…

  • increases number of motor units activated which then…

  • increases number of muscle fibers participating in contraction which then…

  • causes a generation of an increase in muscle tension

Asynchronous recruitment

• Motor units alternate between contraction & relaxation 

• Why is asynchronous recruitment important? 

  • Prevents fatigue (allows to rest) 

  • Helps maintain posture 

  • Helps maintain muscle tone 

Muscle twitch 

Each fiber participating in the contraction can increase the tension it generates via twitch/wave summation and tetanus

Summation & tetanus 

• Results from increased frequency of stimuli (increased firing rate of somatic motor neurons) 

  • Keeps calcium in sarcoplasm for longer time period 

• Leads to smooth, continuous contraction and an increase in force generated by the fibers in a motor unit 

• Permitted by sustained, high Ca2+