anatomy lab - muscles physiology

Spinal motor neurons

• A skeletal muscle may be supplied by hundreds

• Cell bodies in the ventral horn

• Axons leave the spinal cord in the ventral root

Skeletal muscle fiber

• Multinucleate cell

• striated

• voluntary

• Receives synaptic input from only one motor neuron

  • That synapse is the only source of excitation for the fiber

Motor unit

• A motor axon/neuron plus the muscle fibers it connects with

• Action potential in the motor neuron → action potential in all its fibers → single twitch

do the nerve endings and muscle cells touch?

• NO - the gap is the synaptic cleft of the neuromuscular junction

Events at the neuromuscular junction

1. Action potential arrives at synaptic knob

2. Calcium enters synaptic knob

3. ACh released

4. ACh binds ACh receptors

5. End-plate potential forms

6. Muscle action potential

7. ACh removed from synaptic cleft

What starts the events at the neuromuscular junction?

• Action poential travels down the motor neuron axon

• Reaches the axon terminal (synaptic knob)

After the action potential reaches the synaptic knob, what happens?

• Voltage-gated calcium channels in the synaptic knob open

• Calcium diffuses into the terminal

After calcium enters the synaptic knob, what happens?

• Synaptic vesicles release ACh by exocytosis

• ACh enters the synaptic cleft

After ACh is released into the synaptic cleft, what happens?

• ACh diffuses across the synaptic cleft

• Binds to ACh receptors on the motor end plate

• Ligand-gated (chemically gated) sodium channels open

After the ligand-gated sodium channels open, what happens?

• Na⁺ enters and K⁺ leaves the muscle fiber

• More Na⁺ in than K⁺ out → membrane potential becomes less negative

• This graded potential is the end-plate potential

How do the events at the neuromuscular junction end?

• Signal continues until ACh is removed from the synaptic cleft

• By diffusion or breakdown by acetylcholinesterase

Acetylcholinesterase

• Enzyme that breaks down ACh into acetic acid and choline

• Choline is taken back into the axon terminal to make new ACh

Botulinum neurotoxin

• Blocks exocytosis (release) of ACh at the neuromuscular junction

• No end-plate potential can form → no muscle contraction

• Action potential still reaches the synaptic knob and calcium still enters

Motility

• Fundamental life process

• Carried out by filamentous proteins: actin, myosin, and tubulin

• Muscle uses it for locomotion and transport of fluids through tubes of digestive, circulatory, and glandular systems

Three types of muscle

• Smooth

• Cardiac

• Skeletal

• Differ in function, structure, and distribution

• Can be described as voluntary/involuntary, striated/nonstriated, uninucleate/multinucleate

Smooth muscle

• Sheets of cells, each with one nucleus

• Involuntary

• Nonstriated

• Found in walls of blood vessels, digestive tract, and reproductive system

Cardiac muscle

• Found only in the heart

• Uninucleate cells bound together at dense plaques called intercalated disks

• Striated

  • Due to parallel arrangement of bundles of contractile fibers

• Involuntary

Skeletal muscle

• Only voluntary muscle type

• Generally attached to the skeleton

• Cells fused into multinucleated fibers

  • Gives maximum strong, directional contraction

• Prominent striations visible in light microscope

  • Due to extreme regularity of arrangement of contractile proteins

muscle

• is a complex tissue that is comprised of several levels of organization

• composed of fibers (muscle cells), which are made of myofibrils

what are muscle fibers?

• muscle cells which are made of myofibrils

myofibrils

• made of sarcomeres, which are made of myofilaments

what is the order from greatest to least in size discussed in the background of this chapter?

• muscle → fiber → myofibril → sarcomere → myofilament

sarcomeres

• since they are the smallest units of contraction within the muscle fiber, they are considered to be functional units of skeletal muscle

• made of thick myosin and thin actin - both are contractile proteins arranged in alternating pattern

what are the borders of a sarcomere?

• z disc to z disc

thick filaments

• reach from one side of the A band to the next side of the A band

• the myosin heads project to the binding sites on the thin filaments to form cross bridges

fascicle

A small bundle of muscle fibers within a muscle

Layer of connective tissue that surrounds an individual muscle fiber

endomysium

what is the thin filament attached to?

• one end to the Z line and one end not entirely over to the A band

• since it does not reach all the way over there is an area in the middle of the A band that is lighter because there is only thick filament - H zone

h zone

• area in A zone where thin filament does not reach all the way over so it is only thick filament - lighter looking

what is the area of a sarcomere with only thin filament?

I band

M line

• Center of the sarcomere

• Anchors thick filaments in place

Titin

• Protein that makes up elastic filaments

• Runs through the core of thick filaments and attaches them to Z discs at either end

• Resists overstretching and recoils like a spring after the muscle is stretched

what are the regulatory proteins in a sarcomere?

troponin and tropomyosin

where are regulatory proteins found?

• troponin and tropomyosin are found on top of actin thin filaments

Tropomyosin

• Protein that covers myosin binding sites on actin in a relaxed cell

• Bound to troponin

Troponin

• Protein bound to tropomyosin

• Calcium binds to it to start contraction

Zone of overlap importance

• Where thick and thin filaments overlap and cross-bridges form

• More overlap (up to optimal) → more cross-bridges → more tension

Three phases of muscle contraction

• 1. Excitation of the muscle cell

  • ACh released at neuromuscular junction → end-plate potential

• 2. Excitation-contraction coupling

  • Action potential travels along sarcolemma and down T tubules → calcium released from SR

• 3. Cross-bridge cycling

  • Calcium binds troponin → tropomyosin moves → cross-bridges form and power stroke causes contraction

excitation contraction coupling

• Physiological process that converts an action potential in a muscle fiber into a mechanical muscle contraction

• Stimulated by a motor neuron

  • Stimulates several muscle fibers when it generates action potentials

• Motor neuron + the muscle fibers it stimulates = motor unit

Excitation-contraction coupling steps

• Action potential travels from neuromuscular junction (end plate) along sarcolemma

• T tubules conduct it into the interior of the muscle fiber

• Activates voltage-sensitive dihydropyridine (DHP) receptors

• DHP receptors open calcium channels in sarcoplasmic reticulum membrane

• Calcium flows into the sarcoplasm and triggers contraction

t tubules

infoldings of the sarcolemma

T tubules make contact with the SR, and at those connections there are sac-like bulges called?

• Terminal cisternae

• Linked together by calcium-regulating proteins

• Store calcium that is released into the sarcoplasm during excitation-contraction coupling

What is stored in the SR terminal cisterns and released into the sarcoplasm during excitation-contraction coupling?

Ca²⁺

Sarcoplasmic reticulum (SR)

• Stores calcium in resting muscle

• Releases calcium into cytoplasm when an action potential arrives

• Takes calcium back up during relaxation

General requirements for muscle contraction

• Na⁺: enters the cell to create the action potential

• Ca²⁺: binds troponin to expose binding sites on actin

• ATP: powers the cross-bridge cycle and the return of calcium to the SR

Role of calcium in contraction

• Calcium attaches to troponin

• Troponin-tropomyosin complex shifts so tropomyosin moves

  • Uncovers myosin binding sites on actin

• Myosin heads can then bind

• Binding sites stay exposed as long as calcium stays high in the sarcoplasm

Under what conditions will myosin binding sites remain available for myosin heads to attach, initiating another cycle?

a high concentration of calcium is present in the sarcoplasm

Cross-bridges

• Link formed when an activated myosin head binds to actin

• Repeatedly form and break during contraction, creating tension

During contraction, portions of the sarcomere decrease in length, increase in length or stay the same, which ones decrease?

I band and H zone

Cross-bridge cycle

• Before it begins: myosin head is activated (cocked) by ATP

• Step 1: cross-bridge formation

  • Activated myosin head binds to actin to form a cross-bridge

  • Inorganic phosphate is released

  • Bond between myosin and actin becomes stronger

• Step 2: power stroke

  • ADP is released

  • Activated myosin head pivots, sliding the thin filament toward the center of the sarcomere

• Step 3: cross-bridge detachment

  • Another ATP binds to the myosin head

  • Link between myosin head and actin weakens and the head detaches

• Step 4: reactivation of the myosin head

  • ATP is hydrolyzed into ADP and inorganic phosphate

  • Energy released energizes the myosin head and returns it to the cocked position

• Cycle repeats as long as calcium and ATP are present

Sliding Filament Theory

• Cross-bridges pull thin filaments toward the center of the sarcomere

• Changes the filaments' position, NOT their length

• Z discs are pulled along → sarcomere shortens

  • Shortens the muscle fiber and ultimately the entire muscle

3 functions of ATP in muscle

• Detaches the cross-bridge

  • ATP binding weakens the myosin-actin link so the head lets go (cycle step 3)

  • Without ATP, heads stay stuck to actin (rigor mortis)

• Reactivates the myosin head

  • ATP hydrolysis energizes the head and returns it to the cocked position (cycle step 4)

• Returns calcium to the SR

  • Powers active transport of calcium back into the SR, ending contraction

Rigor mortis

• Example of ATP's role in breaking actin-myosin bonds

• After death, ATP declines

• Calcium pumps stop working without ATP, so calcium stays high and the binding sites stay exposed

• Actin and myosin can still bind, but bonds can't break

  • Filaments stay bound → rigid muscle

• Temporary; goes away as decomposition breaks down contractile proteins

Relaxation

• Calcium ions are actively transported back into the SR

  • Cross-bridge formation ends

• Troponin returns to its original shape

• Tropomyosin glides over and covers the myosin binding sites on actin

• Filaments return to their original position

Effects of glycerination

• Makes membranes permeable

• Low-molecular-weight material is extracted

• Contractile proteins remain

• Side effect: troponin-tropomyosin disrupted

  • Myosin heads bind actin without Ca²⁺

• Lets us add different solutions to find requirements for contraction

Requirements for glycerinated muscle contraction

• ATP and Mg²⁺

• Ca²⁺ not needed because troponin-tropomyosin is disrupted

Glycerinated muscle results

• Mg²⁺ alone: no contraction

• ATP alone: some contraction

• ATP and Mg²⁺: most contraction

Role of Mg²⁺ in contraction

• Binds with ATP to form Mg-ATP

• Mg-ATP is the form of ATP myosin uses

Transducer vs. electrode

• Transducer: measures the force of muscle contraction

• Electrode: electrically stimulates the muscle

  • Simulates nerve impulses normally coming from the brain

Threshold stimulus

• Smallest stimulus that produces a contraction

• Below threshold, no force is generated

  • In lab: 0.2 V produced 0 g of force

Maximal stimulus

• Smallest stimulus that produces the maximum response (all motor units recruited)

• Any stronger stimulus produces the same maximal response

• In lab: 1.6 V and above all produced 235 g of force

Recruitment

• Nervous system controls the number of motor axons firing

• Controls number of active motor units → number of contracting fibers

• higher voltage → more motor units recruited → stronger contraction, up to a maximum

motor unit recruitment

the successive activation of additional motor units. The higher the recruitment the stronger the force of the muscle contraction will be

Ways to increase contraction strength

• Stimulate more fibers (recruitment)

• Increase frequency of stimulation

  • Stimuli close together produce stronger contractions

• Muscle length just before stimulation

  • Closest to optimal length → most tension

Length-tension relationship

• Tension depends on number of cross-bridges between thick and thin filaments

• Stretching a muscle stretches its sarcomeres and changes filament overlap

• Already contracted (too short)

  • Thick filaments butt up against Z discs and stop

  • Contraction is brief and weak

• Optimal length (resting length)

  • Overlap is maximized → most tension

• Overstretched

  • Little overlap, so myosin can't grip the thin filaments

  • Contraction is weak

Active vs. passive tension

• Total tension = active + passive; both vary with muscle length

• Active tension: force from thick filaments pulling on thin filaments (cross-bridge cycling)

• Passive tension: occurs during stretch beyond the normal range of motion

  • Resisted by noncontractile proteins, especially titin

  • Collagen and elastin in connective tissue also contribute

• At optimum length, active tension makes up most of total tension

• When overstretched (little or no overlap), passive tension contributes significantly and can exceed active tension

Length-tension: length that produced maximum tension?

• About 28 mm

• Tension increased to a maximum, then decreased as stretch increased

• In lab, data peaked at 28.5 mm

Since the tension produced by a contracting muscle fiber depends upon the number of cross-bridges formed between the thick and thin myofilaments, then stretching the muscle beyond 28.5 mm will lead to what?

decreases the amount of overlap and decreases the amount of tension produced by a single contraction

What keeps muscles near resting length in the body

• Bones and joints

• Prevent excessive shortening and lengthening so maximum tension can be achieved

Refractory period in skeletal muscle

• Brief (a few milliseconds)

• Lets the muscle be stimulated in quick succession

• Makes summation and tetanus possible

Twitch

• Contraction from a single action potential

• One cycle of contraction followed by relaxation

• Weak and usually not observed

• Produces jerky movement; only a fraction of the tension fibers can produce

• Example: spontaneous, involuntary, rhythmic movements of fingers or eyelids

Stages of a single twitch

• Latent period

  • Short delay after the stimulus before tension begins

  • Action potential spreads across sarcolemma and down T tubules; calcium is released from SR

• Contraction phase

  • Calcium binds troponin and cross-bridges cycle

  • Tension rises to its peak

• Relaxation phase

  • Calcium is pumped back into the SR and cross-bridges stop forming

  • Tension falls and the muscle returns to resting length

Twitch: what does the muscle do between single twitches?

• Returns to resting length before contracting again

Why a single twitch can't reach maximum tension

• Calcium channels close and SR quickly takes calcium back up

• Elevated intracellular calcium is brief

• Thick and thin filaments can't slide to maximum capacity

Treppe

• "Staircase effect"

• Muscle is stimulated repeatedly and fully relaxes between stimuli

• Each twitch is slightly stronger than the one before for the first several twitches, then levels off

• Thought to be due to calcium building up in the sarcoplasm and the muscle warming up

• Different from summation because the muscle fully relaxes between twitches

Summation

• Second action potential occurs before relaxation from the first is complete

• Second contraction builds on the first → greater strength

• Muscle does not return to resting length before contracting again

Incomplete tetanus

• Happens as stimulation frequency increases

• Fluttering, sustained contraction

• Single contractions still visible

• Creates more tension than single twitches

• Due to intracellular calcium accumulation

Complete tetanus

• Frequency increases further so no relaxation occurs

• Smooth, sustained, maximal (fused) contraction

• Single contractions can't be seen

• Only reached at unnaturally high frequencies produced in the lab

How tetanus reaches maximum tension?

• Elevated intracellular calcium is maintained

• Filaments have time to slide to fullest capacity

• Tested in Exercise C with pairs of shocks at different intervals on frog gastrocnemius

Why relaxation is slower after tetanus?

Large amount of calcium in cytoplasm takes time for SR to take back up

What was the time interval between stimuli when single twitches were observed?

greater than 250 ms

Why would the rate of muscle relaxation be slower after tetanus than after a single twitch?

It takes time for the large amount of calcium in the sarcoplasm to be taken up by the sarcoplasmic reticulum

if there is only a single twitch induced at a low stimulus rate, that is because…

the stimuli were not frequent enough to cause summation

Stimulation interval results

• Longer intervals → muscle relaxes between stimuli; shorter intervals → contractions combine

• 250 ms (4 stimuli/sec): single twitches

  • Muscle completely relaxed before each stimulus; each twitch had the same force

• 120 ms (about 8 stimuli/sec): summation

  • Muscle only partially relaxed; contractions had more force than single twitches

• 70 ms (about 14 stimuli/sec): complete tetanus

  • Maximal, sustained contraction