Lecture 11

Skeletal muscle functions

Produce movement; protection and support (hold organs in place); maintain posture and stabilize joints; generate heat; communication (speaking, facial expressions, gestures, typing/writing)

Muscle function

Heat generation: When muscles work, some of the energy used is converted to heat

Contractility

Muscle characteristic: ability to forcibly shorten when stimulated

Excitability

Muscle characteristic: ability to receive and respond to a (chemical) stimulus

Extensibility

Muscle characteristic: ability to stretch beyond resting length

Elasticity

Muscle characteristic: ability to recoil and resume resting length

Plasticity

The "plus one" muscle characteristic: constantly adapts based on usage

Skeletal muscle as an organ

Each skeletal muscle is a discrete organ; over 600 named skeletal muscles in the body

Epimysium

Connective tissue layer surrounding the whole muscle

Perimysium

Connective tissue layer surrounding bundles of muscle fibers; the bundle is a fascicle

Fascicle

Bundle of muscle fibers surrounded by perimysium

Endomysium

Connective tissue layer surrounding each individual muscle fiber

Three concentric CT layers of muscle (outer to inner)

Epimysium (whole muscle), perimysium (fascicles), endomysium (individual fibers)

Tendon

Thick cordlike dense regular CT; attaches muscle to bone, skin, or muscle; formed by convergence of the three CT layers; extends beyond muscle fibers; attached to periosteum

Sarcolemma

Plasma membrane of the muscle fiber

Sarcoplasm

Cytoplasm of the muscle cell; contains glycosomes (stored glycogen), myoglobin (stores O2), many mitochondria; multinucleated

Glycosomes

Stored glycogen granules in the sarcoplasm

Myoglobin

Stores O2 in muscle; increases rate of O2 transfer from blood to muscle

Triad

T-tubule flanked by two terminal cisternae of the sarcoplasmic reticulum

Transverse tubules (T-tubules)

Membranous tubes perpendicular to fiber length; conduct the action potential from the cell surface through the cell

Sarcoplasmic reticulum (SR)

Modified smooth ER; surrounds each myofibril like a mesh sleeve; stores high Ca2+ released for contraction

Terminal cisternae

Blind-ended sacs at the ends of SR adjacent to T-tubules; reservoir for Ca2+

Myofibril

Highly organized cytoskeleton; hundreds to thousands per cell; extends the whole length of the cell; made of myofilaments

Myofilaments

Thick filaments (myosin) and thin filaments (actin, tropomyosin, troponin)

Thick filament

Assemblage of myosin; two halves with myosin oriented in opposing directions, heads facing outward

Myosin structure

Protein with 2 identical subunits: intertwined long tails and 2 globular heads

Myosin head functional sites

Actin-binding site and ATPase site; heads form cross-bridges

Thin filament

Assemblage of actin (F-actin) plus tropomyosin and troponin

F-actin

Two strands of G-actin molecules forming a helix; has myosin-binding sites

Tropomyosin

Long chain on actin that "hides" the myosin binding site at rest

Troponin

Bridges tropomyosin and actin; binds Ca2+

Sarcomere

Functional unit of muscle; area between two Z lines

Z line (Z disc)

Cytoskeletal disc interconnecting actin filaments; marks sarcomere boundaries

Muscle growth in length

By adding more sarcomeres, not by lengthening each sarcomere

I band

Thin filaments not extending into the A band; projects from Z lines; shortens during contraction

A band

Region of thick filaments plus overlapping thin filaments; stays the same length during contraction

H zone

Within the A band; thick filaments only; shortens during contraction

M line

Transverse proteins interconnecting thick filaments; center of A band and H zone

Nebulin

Inelastic protein that helps align actin filaments; attached to Z disks

Titin

Single-stranded elastic protein from M line to Z line along thick filament; spring that passively recoils the cell to resting length; stabilizes thick filament position

Dystrophin

Protein complex anchoring myofibrils near the sarcolemma to the sarcolemma

Alpha-actinin

Crosslinks antiparallel thin filaments

Motor unit

A single alpha motor neuron plus the muscle fibers it innervates

Motor unit size and precision

Delicate activity = few fibers per motor unit; coarse activity = many fibers per motor unit

Motor unit fiber distribution

Fibers are dispersed (not clustered) throughout the muscle, so stimulation gives an evenly distributed contraction (twitch)

Neuromuscular junction (NMJ)

Where the motor neuron meets the muscle fiber; each skeletal muscle fiber has just one

Synaptic knob

Terminal end of motor neuron axon; holds synaptic vesicles with acetylcholine (ACh)

Motor end plate

Specialized sarcolemma under the synaptic knob; contains ACh receptors (chemically gated ion channels)

Synaptic cleft

Space between synaptic knob and motor end plate; contains acetylcholinesterase (AChE), which breaks down ACh

Acetylcholinesterase (AChE)

Enzyme in the synaptic cleft that breaks down ACh

Muscle twitch

A single contraction in a muscle fiber

Latent period

Time delay between stimulation and beginning of contraction (the action potential is already over)

Contraction time (twitch)

From onset of contraction to peak tension

Relaxation phase (twitch)

From peak tension back to rest; roughly equal to contraction time

Why twitches matter

A single twitch is too weak and brief to be useful; twitches used cooperatively and additively produce contraction

Three steps in muscle contraction

Initiation (excitation and Ca2+ release), cross-bridge formation/powerstroke, and contraction (sliding filament); followed by relaxation

Initiation of muscle contraction

Step 1 (motor neuron): Action potential arrives at synaptic knob; Ca2+ enters knob; ACh released | Step 2 (muscle cell): ACh binds receptor; Na+ rushes in producing end-plate potential (EPP); action potential initiated and propagates along the cell and down T-tubules | Step 3 (T-tubule to SR): AP down T-tubules opens DHP channels (voltage-gated L-type Ca2+ channels), which open RyR channels on the SR; Ca2+ flows into cytoplasm

End-plate potential (EPP)

Depolarization of the motor end plate caused by Na+ entry after ACh binds its receptor

DHP channels

Voltage-gated L-type Ca2+ channels in T-tubule membrane; coupled to RyR channels

RyR channels

Channels on the SR that open when DHP channels open; release Ca2+ into the cytoplasm

Cross-bridge formation

Ca2+ released from SR binds troponin; tropomyosin pulled away from actin's myosin-binding site; myosin binds actin

Powerstroke

Cocking: Myosin ATPase hydrolyzes ATP to ADP + Pi, cocking the myosin head | Pull: Myosin binds actin (if site is available); powerstroke occurs and ADP + Pi are released | Release: New ATP binds myosin's ATPase site, causing myosin to release from actin

Role of ATP in cross-bridge cycling

ATP hydrolysis cocks the head; ATP binding detaches myosin from actin

Sliding filament mechanism

Thin filaments slide inward over stationary thick filaments toward the center of the A band; pulls Z lines closer, shortening the sarcomere

Sarcomere changes during contraction

H zone shorter, I band shorter, A band unchanged; filaments themselves do not shorten

Relaxation

ACh removal: AChE removes ACh so no EPP and no action potential | Ca2+ removal: SERCA (Ca2+-ATPase on the SR) pumps Ca2+ from cytosol back into SR; actin and myosin can no longer interact

SERCA

Ca2+-ATPase pump on the SR that actively pumps Ca2+ from cytosol into the SR

Muscle ATP supply overview

Limited ATP stored; three sources: phosphagen system (immediate), anaerobic respiration (short-term), aerobic respiration (long-term)

Phosphagen system

Immediate ATP; no oxygen needed; used early and quickly

Stored ATP in muscle

About 5-6 seconds of energy

Myokinase

Transfers Pi from one ADP to another ADP to make ATP; about 2 seconds of energy

Creatine phosphate

Storage form of Pi; creatine kinase transfers Pi between creatine phosphate and ADP to make ATP; provides 10-15 seconds of energy

Creatine kinase

Transfers Pi between creatine phosphate and ADP to make ATP (reverse reaction stores energy)

Anaerobic cellular respiration (short-term)

Uses glycogen stored in muscle; glycolysis pyruvate converted to lactic acid instead of entering TCA; rapid; the last resort

Aerobic cellular respiration (long-term)

Requires O2; relatively slow and depends on nutrient delivery; high ATP yield; myoglobin speeds O2 transfer

Order of energy systems in time

Phosphagen (seconds), anaerobic respiration (short-term), aerobic respiration (long-term)