Muscles

Ch.12 Our patient for the day... Name: Eddy Age: Newborn

Whole-body muscle contractions

No relaxation

Severe difficulty breathing due to inadequate relaxation of breathing muscles

Diagnosed with tetanus Stepping on a rusty nail with a certain type of bacteria can be baaaaaad

Let’s talk about why. Our patient for the day... Name: Eddy Age: Newborn

Whole-body muscle contractions

No relaxation

Severe difficulty breathing due to inadequate relaxation of breathing muscles

Diagnosed with tetanus Signaling a muscle to start contraction

ACh Nicotinic receptor

Target: CNS Figure 8.19a ESSENTIALS – Synaptic Communication

Neurotransmitter Release

An action potential depolarizes the axon terminal.

Synaptic vesicle Action potential with neurotransmitter The depolarization opens arrives at molecules voltage- gated Ca2+ channels, axon terminal and Ca2+ enters the cell.

Calcium entry triggers exocytosis of synaptic vesicle contents. Docking protein 2+ Ca Neurotransmitter diffuses Synaptic across synapse and binds to cleft post-synaptic receptors.

Neurotransmitter binding initiates a response in the postsynaptic cell. Voltage-gated Receptor 2+ Postsynaptic cell Ca channel Cell response

If this Somatic Motor Pathways Trigger Action Potentials Within Skeletal Muscle

Synaptic vesicle (ACh)

Ca2+ Ca2+

ACh Acetyl + choline Voltage-gated Ca2+ channels

AChE

Nicotinic receptors bind Skeletal muscle ACh, opening Na+ channels, fiber triggering action potentials and contraction in skeletal muscle. Why do APs in the muscle cause them to contract? To learn about something’s function, we can start by taking a look at its structure.

Let’s take a look under the microscope Anatomy review Skeletal muscle composed of many of muscle fibers/cells

Tendon Skeletal muscle (connects bone to muscle) Nerve and blood vessels Connective tissue

Muscle fascicle: bundle of fibers Connective tissue

Nucleus

Muscle fiber Skeletal muscle composed of many of muscle fibers/cells

Tendon Skeletal muscle (connects bone to Whole muscle muscle) Nerve and blood vessels Muscle fascicle Connective tissue

Muscle fiber/cell Muscle fascicle: bundle of fibers Connective tissue

Nucleus

Muscle fiber Figure 12.1

THE THREE TYPES OF MUSCLES HAVE DIFFERING STRUCTURES/APPEARANCES

Skeletal muscle fibers are large, multinucleate cells that appear striated (striped) under the microscope. Control the Nucleus movement of our skeleton

Muscle fiber (cell)

Striations *multinucleated=many nuclei in same cell

Cardiac muscle fibers are also Nucleus striated but they are smaller, branched, and uninucleate. Cells are joined in series by junctions Muscle fiber called intercalated disks.

Intercalated disk

Striations

Smooth muscle fibers are small, uninucleate, and lack striations.

Nucleus

Muscle fiber The basic functional unit of a myofibril is the A band Sarcomere Z disk Z disk

ANATOMY SUMMARY

M line I band H zone

Titin

Z disk Z disk M line crossbridges

M line Thick filaments Thin filaments A band: overlap of thick and thin filaments

I band: only thin filamentsTitin

Troponin Myosin heads

Hinge Myosin tail region

Tropomyosin G- molecule

Myosin molecule Actin chain The basic functional unit of a myofibril is the sarcomere A band Sarcomere Z disk Z disk

ANATOMY SUMMARY Myofibril

M line I band H zone

Titin

Z disk Z disk M line Myosin crossbridges

M line Thick filaments Thin filaments

Titin

Troponin Nebulin Myosin heads

Hinge Myosin tail region

Tropomyosin G-actin molecule

Myosin molecule Actin chain Muscle cells and tissue use unique names for some common things End anatomy review Muscle fibers composed of subunits called myofibrils

Mitochondria (energy source)

Sarcoplasmic reticulum

Nucleus Thick Thin filament filament

T-tubules Now let’s look at one individual muscle fiber/cell and its part Myofibril

Sarcolemma=Cell membrane Sarcoplasmic Retic.=Modfied Endoplasmic Reticulum T-tubules=invaginations of sarcolemma Muscle fibers composed of subunits called myofibrils

Mitochondria (energy source) (Ca2+ storage)

Nucleus

T-tubules

Sarcolemma (cell membrane)

Sarcolemma=Cell membrane Sarcoplasmic Retic.=Modified Endoplasmic Reticulum T-tubules=invaginations of sarcolemma Figure 12.10a ESSENTIALS – Excitation-Contraction Coupling and Relaxation Slide 2 https://www.youtube.com/watch?v=8Hu5W_tFXLs

Axon terminal of somatic motor neuron KEY DHP = dihydropyridine L-type calcium channel

RyR = ryanodine receptor-channel Muscle fiber ACh nt ial Let’s look in a bit more detail about how e

Somatic motor neuron releases calcium+ gets released from the sarcoplasmic Na ACh a .

Action pot pot Action reticulum.... Motor end plate + RyR Net entry of Na through ACh receptor-channel initiates a T-tubule muscle action potential. Ca2+ Sarcoplasmic reticulum Z disk DHP Troponin Actin Tropomyosin M line Myosin head

Myosin thick filament

© 2013 Pearson Education, Inc. Figure 12.4 T-TUBULES HELP SPREAD ACTION POTENTIAL IN FIBER T-tubules are extensions of the cell membrane (sarcolemma) that associate with the ends () of the sarcoplasmic reticulum.

T-tubule brings action potentials into interior Sarcoplasmic of muscle fiber. reticulum stores Ca2+. Sarcolemma AP in muscle fiber

Triad Thick Thin Terminal filament filament cisterna Figure 12.10b ESSENTIALS – Excitation-Contraction Coupling and Relaxation Slide 5 https://www.youtube.com/watch?v=IOkn1ldFO60

DHP KEY DHP = dihydropyridine L-type calcium channel

RyR = ryanodine receptor-channel RyR

Action potential in t-tubule Let’s look in a bit more detailalters conformationabout ofhow DHP calcium gets released from thereceptor. sarcoplasmic DHP doesn’t open! DHP receptor opens RyR Ca2+ RyR reticulum.... release channels in sarco- DHP plasmic reticulum, and Ca2+ enters cytoplasm.

Ca2+ released Ca2+ binds to troponin, allowing actin-myosin binding.

Myosin thick filament Myosin heads execute power stroke.

Distance actin moves Actin filament slides toward center of sarcomere.

© 2013 Pearson Education, Inc. Figure 12.8b (2 of 7) Slide 5 Figure 12.10b ESSENTIALS – Excitation-Contraction Coupling and Relaxation https://www.youtube.com/watch?v=sIH8uOg8ddw Slide 5

2+ Cytosolic Ca2+ Ca levels increase in cytosol. DHP Tropomyosin KEY shifts, exposing DHP = dihydropyridine L-type binding site on Ca 2+ binds calcium channelto actin. troponinRyR = ryanodine (TN). receptor-channel RyR

Action potential in t-tubule Let’s look in a bit more detailTroponin-Caalters conformationabout2+ ofhow DHP TN complexreceptor. DHP pulls doesn’t open! calcium gets released from thetropomyosin sarcoplasmic Actin 2+ awayDHP receptor from opensactin RyR’s Ca RyR reticulum....moves release channels in sarco- myosin-binding site.2+ DHP ADP plasmic reticulum, and Ca enters cytoplasm. Power stroke Ca2+ released P Ca2+ binds to troponin, i Myosinallowing actin-myosin binds strongly binding. to actin and completes power stroke. Myosin thick filament Myosin heads execute power stroke.

Distance actin moves ActinActin filament filament slides toward moves.center of sarcomere. See video for how myosin uses ATP to complete power stroke © 2013 Pearson Education, Inc. © 2013 Pearson Education, Inc. After death, an animal can experience rigor mortis, the state of rigidity due to sustained ....even after death.

Rigor mortis is due to lack of production of ATP. WTH?!

NO ATP leads to sustained muscle contraction?!?!

Let’s watch the video again... https://www.youtube.com/watch?v=sIH8uOg8ddw A normal at rest (no sarcoplasmic Ca2+, ATP hydrolyzed into ADP + P by myosin)

Ca2+ released Ca2+ not released

A normal excited, muscle cell Binding sites for myosin unexposed, (sarcoplasmic retic. Ca2+ released) No contraction A normal excited, muscle cell (sarcoplasmic retic. Ca2+ released) Myosin binds to actin

ATP present? Myosin detaches and hydrolyzes ATP. Myosin resets

If Ca2+ still around too, generate another power stroke

Myosin releases ADP and P, generates power stroke/force A normal excited, muscle cell (sarcoplasmic retic. Ca2+ released) Myosin binds to actin Rigor mortis: hours after death, SR membrane breaks down.

Sarcoplasm Ca2+ Force generated Available ATP Myosin gets stuck in this Myosin releases ADP and P, generates conformation power stroke/force A normal excited, muscle cell (sarcoplasmic retic. Ca2+ released) Myosin binds to actin How do we get the muscle to relax normally?

Myosin releases ADP and P, generates power stroke/force FigureFigure 12.10b12.10c ESSENTIALSESSENTIALS –– Excitation-ContractionExcitation-Contraction Coupling Coupling and and Relaxation Relaxation SlideSlide 5 3

https://www.youtube.com/watch?v=IOkn1ldFO60KEY DHP = dihydropyridine L-type calcium channel KEY RyR = ryanodine receptor-channel DHP = dihydropyridine L-type calcium channel Action potential in t-tubule Let’s look in a bit more detailaltersRyR conformation =about ryanodine receptor-channel ofhow DHP receptor. calcium gets released from theSarcoplasmic sarcoplasmic Ca2+-ATPase DHPpumps receptor Ca2+ backopens into RyR SR. Ca 2+ reticulum.... release channels in sarco- plasmic reticulum, and Ca2+ entersDecrease cytoplasm. in free cytosolic ATP [Ca2+] causes Ca2+ to unbind Ca2+ releasesCa2+ released Ca2+ from troponin. Ca2+ binds to troponin, allowing actin-myosin binding. Tropomyosin re-covers binding site. When myosin heads release, elastic elements pull MyosinMyosin thickthick filamentfilament Myosinfilaments heads back execute to their power relaxed stroke.position.

Distance actinactin movesmoves Actin filament slides toward center of sarcomere. AP stops, RyR closes, Ca2+ return > Ca2+ release: Muscle relaxes © 2013 Pearson Education, Inc. © 2013 Pearson Education, Inc. You have decided to move your arm. So, you need to send an efferent signal to your arm from your CNS and make your arm muscle contract. Which ion is most important for triggering muscle contraction during this whole process?

A.) K+ B.) Na+ C.) Ca2+ D.) Acetylcholine A muscle cell has been depolarized and already is having its action potential. Which ion is most important for triggering muscle contraction after this point?

A.) K+ B.) Na+ C.) Ca2+ D.) Norepinephrine Some unique and interesting properties of muscle fibers 1. Delay between excitation and contraction Figure 12.11

There’s a delay between excitation of the muscle and contraction

Action potentials in the axon terminal (top graph) and in the muscle fiber (middle graph) are Motor Neuron Action Potential followed by a muscle twitch (bottom graph).

+30 Muscle fiber Neuron membrane Action potential potential from CNS in mV

−70

Time

Motor Recording end plate electrodes Axon Muscle Fiber Action Potential terminal

+30 Muscle fiber Muscle action membrane potential potential in mV

−70 2 msec

N A V I G A T O R Time

Neuro- muscular junction Development of Tension During One Muscle Twitch (NMJ)

E-C Latent Contraction Relaxation coupling period phase phase Tension

Muscle twitch 10–100 msec FIGURE QUESTIONS Time Movement of what ion(s) in What’s causing thiswhat direction(s) delay creates between electrical activity (a) the neuronal action potential? and force(b) the generation muscle action potential? in the muscle? Figure 12.10 ESSENTIALS – Excitation-Contraction Coupling and Relaxation

Excitation

Contraction

Lots of steps in between excitation and contraction leads to ~2-3msec delay 2. Energy storage/availability Figure 12.12

Phosphocreatine

Resting muscle stores energy from ATP in the high-energy bonds of phosphocreatine. Working muscle then uses that stored energy.

Muscle at rest

creatine ATP from metabolism + creatine ADP + phosphocreatine kinase

Working muscle

creatine Phosphocreatine + ADP Creatine + ATP kinase

needed for When these reserves are depleted, ATP is made through aerobic and • Myosin ATPase (contraction)

anaerobic glycolysis. • Ca2+-ATPase (relaxation)

• Na+-K+-ATPase (restores ions that cross cell membrane during action potential to their original compartments) 3. Ideal muscle length Figure 12.15 Adapted from A. M. Gordon et al., J Physiol 184: 170–192, 1966.

LENGTH-TENSION RELATIONSHIPS

Too much or too little overlap of thick and thin filaments in resting muscle results in decreased tension.

C

B D

100

80

60

40 A E

20

0 1.3 µ m 2.0 µ m 2.3 µ m 3.7 µ m Tension/Force of max) percentage (as Decreased Increased length length Optimal resting length

Sarco mere l en g th 4. recruitment can help a whole muscle increase force generated Figure 12.17 MOTOR UNITS

A motor unit consists of one motor neuron and all the muscle fibers it innervates. A muscle may have many motor units of different types.

One muscle may have SPINAL CORD many motor units of different fiber types.

Neuron 1 Neuron 2 Neuron 3 Motor nerve

KEY

Muscle Motor unit 1 fibers Motor unit 2

Motor unit 3

How do we get fine motor movement (e.g. hands): only a few muscle fibers per motor unit. Allows for more precise control of movement/fiber activation