Chapter 12

Question 1

Skeletal Muscle

Answer 1

-Skeletal muscles are connected to the bones they move by tough tendons, composed of closely-packed, parallel arrays of [mostly] collagen protein.

contraction is voluntary

As we will see later, contraction of skeletal muscle depends upon stimulation by motor neurons—this is very different from cardiac and smooth muscle, both of which are capable of spontaneous contraction, and are under autonomic control.

Question 2

Myofiber

Answer 2

single cell, containing multiple bundles of contractile elements (“muscle fiber/cell”)

• run from one end of muscle to another
• multiple bound in a fascicles
• multinucleated (all fully functional), mitochondria, SR, T-tubule

Question 3

Major elements of a myofiber:

Answer 3

1) Myofibrils (contractile filaments + regulatory prots)
2) Mitochondria
3) Sarcoplasmic reticulum- contains glycogen (storage form for glucose) granules in glycosomes
4) T-tubules- extension of cell membrane that run all the way through muscle cell

Question 4

Muscle Cell Membrane

Answer 4

sarcolemma

Question 5

muscles cytoplasm

Answer 5

sarcoplasm

-high concentrations of O2 binding protein = myoglobin

Question 6

modified ER

Answer 6

sarcoplasmic reticulum

• plays a major role in excitation-contraction coupling –> the myofiber’s storage repository for calcium
• in response to a signal from a motor neuron, it releases calcium into the sarcoplasm for muscle contraction, then takes that calcium back up during relaxation.

Question 7

what are the muscle contractile units?

Answer 7

myofibrils - bundles of contractile proteins within each muscle cell

Question 8

Striations

Answer 8

These result from:

a) the regular arrangement of the contractile proteins in a given myofibril
b) the fact that parallel myofibrils are arranged in register with each other
c) the fact that all the myofibers are unbranched, i.e. they’re stacked parallel to each other

-muscle cells arranged in parallel, no branching, long, flattened nuclei = more noticeable striations

Question 9

Z disc

Answer 9

center of each I band

Question 10

H band

Answer 10

center of A band with no thin filament overlap

Question 11

I band

Answer 11

only thin filaments, primarily ACTIN

Question 12

A band

Answer 12

thick filament + thin filament overlap

thick filament= MYOSIN

Question 13

Thick vs Thin filaments

Answer 13

Thick= aggregates of myosin—long fibrous “tail” connected to globular “head”

• hundreds of myosin molecules, joined end-to-end, and bundled together, with their “hinged” heads sticking out (form cross-bridge to link with acting to make contractions)
• remain stationary

thin= polymers of actin—made of 300-400 G-actin subunits in double row & twisted to form “double-helix”

-do sliding for contraction

Question 14

sarcomere

Answer 14

the basic cellular unit of contraction

• A single sarcomere extends from one Z-line (disc) to the next.
• There are about 100,000 sarcomeres in your biceps muscle.
• In 3D, the sarcomere forms a hexagonal pattern

Question 15

M lines

Answer 15

center of each A band; protein filaments that help hold down thick filaments

Question 16

Titin

Answer 16

contributes to elastic recoil during relaxation (“spring”)

-runs from Z disc to M line

Question 17

Contraction: Sliding Filament Mechanism

Answer 17

sarcomere’s get shorter

a) A bands do not shorten, but move closer together.
- Z bands get closer together
b) I bands shorten, but thin filaments do not.
c) Thin filaments slide toward H band
d) H band shortens or disappears
- -> muscle gets shorter

–>the thick filaments remain stationary, while the thin filaments slide inward (i.e. towards the M-line, lying at the center of each H-band)

Question 18

Actin Monomer

Answer 18

G-actin (blue spheres) [G = “Globular”]
–> Each actin monomer in the filament has a myosin-recognition site to which an actin-binding site on the globular myosin head (see next slide) can bind. Under resting conditions, this site is obscured–covered up–by the tropomyosin, such that myosin cannot bind.

Question 19

Actin Polymer

Answer 19

F-actin (joined spheres) [F = “Filamentous”]

Question 20

Regulatory Proteins

Answer 20

Troponin & tropomyosin

-Running along the F-actin helices

Question 21

There are three key features of the globular head of myosin which are critical for the mechanism of contraction:

Answer 21

1. The tip of the head has the actin-binding site
2. A second domain on the side of the head has an ATP-binding site, directly linked to a third domain, which has ATPase enzymatic activity
3. The head is connected to the “tail” by a fourth domain which is a hinge, around which the entire head can pivot
   - ->Pivoting of the globular head is triggered by ATP hydrolysis.

Myosin head: myosin ATPase
[ATPADP +Pi]

ATP  ADP + Pi activates
globular myosin head, causing
it to pivot

Question 22

Resting state….

Answer 22

…myosin binding sites on actin are BLOCKED by tropomyosin

–> this prevents crossbridge formation!

Question 23

Calcium

Answer 23

Calcium binds to troponin –> tropomyosin moves away
from the myosin-binding site –> shifts 3D formation

-Ca2+ is critical to contraction—if it’s not present, myosin-actin interactions (crossbridges) cannot form, and no contraction is possible.

Question 24

Sequence of events at a single crossbridge (assume that we start at the end of the previous contraction):

Answer 24

1. The myosin head is bound to the binding site on actin. (by hydrolysis of bound ATP- allows binding of head to actin and “energizes” the head –> cocking head like a trigger)
2. ATP binds to the myosin head—this triggers release from the actin (i.e. the crossbridge is dissolved)
3. ATP is hydrolyzed to ADP—this energizes the myosin head, and it engages with the binding site on actin
4. Release of inorganic phosphate (Pi) causes the myosin head to move, which drags the bound actin along with it.
5. A new ATP molecule binds to the myosin head and the cycle starts again.
   - -> impossible w/o Ca, because tropomyosin MUST be moved away

*After power stroke, ADP is released and a new ATP binds. This makes myosin release actin—and the cycle begins again, continuing until the sarcomere has shortened.

Question 25

Where does Ca come from?

Answer 25

ALL Ca comes from the sarcoplasmic reticulum in skeletal muscle —SR is major reservoir for Ca2+ storage & release

Question 26

Ca and SR

Answer 26

- SR is modified ER that stores Ca2+ when muscle is at rest - Upon stimulation, Ca2+ diffuses out of calcium release channels (ryanodine receptors) - At end of contraction, Ca2+ actively pumped back into the SR. - ->SR is extensive: ensures that all the bundles of myofibrils can be potentially be exposed to a flood of calcium

Question 27

T-tubules

Answer 27

extensions of cell membrane (sarcolemma)that associate with ends (terminal cisternae) of sarcoplasmic reticulum. --> brings action potentials into interior of muscle fiber = important for excitation-contraction coupling -proximity of SR to T-tubules: this ensures that an action potential traveling down the tubule is quickly transduced into a signal for calcium release.

Question 28

How nerves signal a muscle:

Answer 28

1. Neurotransmitter released: acetylcholine depolarizes end-plate region of the muscle fiber -When it binds to its receptor, it triggers opening of a Na+ channel (ligand-gated sodium channel). 2. Na moves in! Depolarization initiates A.P. in the muscle fibercontraction --> that local change in voltage next triggers opening of so-called voltage-gated Na+ channels, they in turn let more Na+ in and that changing voltage is propagated along the membrane (sarcolemma) and passes down into the T-tubules. --> each skeletal muscle fiber is innervated my a different nerve fiber, but be separately stimulated by a single motor neuron (no electrical connection like cardiac muscle)

Question 29

Excitation-contraction coupling in skeletal muscle

Answer 29

conversion of a nerve signal (“excitation”) into a muscle contraction. The molecule that “couples” these two processes is CALCIUM A.P.’s conducted along T-tubules --> voltage-gated Ca2+ channels --> open Ca2+ release channels in s.r.-->  Ca2+ stimulates contraction *volatage-gated Ca channel = dihydropyridine (DHP) receptors For this class I will refer to them as DHP receptors, rather than voltage-gated calcium channels, because they really don’t let calcium in. Instead, they are physically connected to so-called ryanodine receptors that are located in the membrane of the s.r. The ryanodine recptors are calcium release channels. When the DHP receptors are activated by an action potential, they change their conformation and that in turn, open the ryanodine receptors, allowing calcium to flow out of the s.r. into the sarcoplasm, and flood the contractile apparatus with calcium. NOTE: In skeletal muscle, ALL the calcium for contraction comes from the s.r.—none comes from the extracellular space. This is a difference between skeletal and cardiac and smooth muscles—in the latter two muscle types some calcium DOES come from outside, via “L-type calcium channels.”

Question 30

Muscle Relaxation

Answer 30

-Action potentials stop; no further calcium release from s.r. -Active pumping of Ca2+ back into s.r. via SERCA pump (Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase; requires ATP) ATP is required for both initiation & termination of contraction: 1. Unbinding of myosin head from actin at the end of a contraction cycle 2. Energization (activation) of myosin head 3. Pumping of Ca2+ out of sarcoplasm back into s.r.

Question 31

Muscle Contraction Steps

Answer 31

1. Acetylcholine from motor neuron 2. End plate potentials 3. Action potentials (propagated down T-tubules) 4. T-tubule V-gated calcium channels (DHPR) activated 5. Opening of calcium release channels (ryanodine receptor) in s.r. 6. Calcium released, binds to troponin. 7. Contraction

Question 32

Muscle Relaxation Steps

Answer 32

1. Action potentials cease. 2. Calcium release channels close 3. Ca2+-ATPase pumps (SERCA) move Ca2+ back into s.r. 4. No more Ca2+ bound to troponin C 5. Tropomyosin blocks myosin binding sites on actin