Skeletal Muscle Contraction

Question 1

what does the I band contain?

Answer 1

(isotropic light bands) only actin thin filaments, from Z line to center of the sarcomere

Question 2

what does the A band contain?

Answer 2

(anisotropic dark bands) myosin thick filaments

Question 3

what is the H zone?

Answer 3

no overlap between actin and myosin

Question 4

what is the M line?

Answer 4

the center of the sarcomere, where the thick filaments are linked with each other

Question 5

how is the skeletal muscle organized?

Answer 5

muscle > fasicle > fiber/cell > myofibril > myofilament > sarcomere

Question 6

myosin molecule in muscle

Answer 6

6 polypeptide chains

• 2 heavy chains (230KD) intertwined as double helix and ending in 2 globular heads, with a double-coiled helix tail
• 4 light chains (20KD) each in head region

Question 7

myosin heavy chain (not the same as thick filament)

Answer 7

single PRO that contains globular region that binds both actin and hydrolyzes ATP during muscle contraction
-contians hinge region and extended tail region made of two heavy chains wound together

Question 8

regulatory light chain (RLC)

Answer 8

phosphorylated in striated muscles by Ca++/calmodulin-dependent myosin light chain kinase

• maintained in fast-twitch after tetanus or low-frequency repetitive stimulation
• phosphorylation correlates with potential of the rate in development and max extent of isometric twitch tension

Question 9

essential/alkali light chain (ELC)

Answer 9

provides fine tuning of the myosin motor function, regulated in an isoform and tissue-dependent manner

Question 10

myosin/thick filament

Answer 10

1. 6 micron length (equal to A-band) made of 200+ individual myosin molecules that point outward from central H-zone
   - successive myosin heads are axially displaced from previous by 120 degrees, so heads protrude in all directions from the tail
   - each myosin head has an ATPase catalytic site and actin binding site

Question 11

outline of excitation contraction coupling

Answer 11

1. motor ATP travels along motoneuron to motor endplate at neuromuscular junction
2. nerve endings secrete ACh that acts on local area of sarcolemma to open numerous ACh-gated ion channels
3. Na+ flows into muscle to depolarize muscle membrane potential, initiating AP to propagate along membrane
4. AP propagates down T-tubule into interior of muscle fiber to triad junction, where it causes release of Ca++ ions that have been sequestered in longitudinal SR
5. increased [Ca++] causes actin and myosin filaments to interact w/ each other, causing sliding motion to shorten length of sarcomere
6. Ca++ are pumped back into SR by Ca-ATPase ion pump in SR membrane, reducing [Ca++] in sarcoplasm, allowing relaxation
7. lengthening of muscle due to antagonistic muscle contraction (biceps VS triceps)

Question 12

what is a triad made of?

Answer 12

2 cisternae and 1 T-tubule (both from sarcoplasmic reticulum)

Question 13

tropomyosin

Answer 13

alpha-helical rod that covers the myosin binding sites on the thin filament in resting muscle
blocks myosin from binding to the actin thin filament
-bound to by troponin T

Question 14

troponin and its components

Answer 14

complex of 3 PRO subunits that binds tropomyosin to thin filament

• C - binds Ca++
• I - inhibits actomyosin ATPase and binds to actin
• T - binds to tropomyosin
• when C binds Ca++, tropomyosin moves and uncovers active sites in actin, allowing interaction

Question 15

crossbridge cycle steps

Answer 15

1. ATP binds to myosin causing tilted X-bridge to separate from actin
2. myosin ATPase cleaves ATP, but hydrolysis products ADP and phosphate remain bound to myosin
   - cleavage of ATP causes X-bridge, still separated from actin, to change conformation to perpendicular “cocked” orientation
3. “X-bridge” forms as myosin head binds to actin
4. myosin head then releases phosphate, causing conformational change in X-bridge to tilted position, allowing power stroke that drags actin filament towards M-line
5. ADP released in final step of the cycle

Question 16

how much of the energy stored in ATP is transformed into mechanical work?

Answer 16

30% of energy

Question 17

isometric contractions

Answer 17

occur at constant muscle length

Question 18

how to measure force generated during isometric twitch?

Answer 18

muscle is fixed so force measured w/o muscle shortening

• stimulate electrically with single AP, and force generated is measured as a function of time
• latent period between stimulation and contraction (time delay between AP and activation of X-bridge cycle)
• tension builds during contraction phase of twitch and tension declines during relaxation phase

Question 19

what do the contraction and relaxation phases of muscle closely parallel?

Answer 19

the levels of Ca++ in sarcoplasm that surrounds sarcomere

Question 20

what is a “muscle twitch”?

Answer 20

contraction generated by a single AP

-basis of muscle contraction and heart contracts by “twitch” only

Question 21

fast and slow twitch muscle

Answer 21

number of factors dictate different kinetics between isometric twitches including type of myosin heavy chain expressed and speed of sarcoplasmic Ca++ elevation and clearance
-fast twitches develop and relax quickly

Question 22

slow twitch (type I) MYH genes

Answer 22

MYH7

fatigue-resistant, red myoglobin, oxidative metabolism, high mitochondria and low glycogen

Question 23

fast twitch (type IIa and IIb) MYH gene

Answer 23

a: MYH2; fatigue-resistant, red myoglobin, oxidative metabolism, most mitochondria and high glycogen
b: MYH4; susceptible to fatigue, white b/c low myoglobin, glycolytic metabolism, few mitochondria, and high glycogen

Question 24

what does MYH mean?

Answer 24

myosin II heavy chain gene

Question 25

what does the amount of tension generated reflect?

Answer 25

the degree of overlap of thick and thin filaments

• tension increases as degree of overlap of thin and thick filaments increases
• if sarcomere stretches too far, there are fewer X-bridges and thus less force generated (less tension)
• -also if muscle shortened below optimal length, or actin crosses M-line and interferes with formation of X-bridges on other side of sarcomere

Question 26

when is the muscle at its optimal length/tension?

Answer 26

when the number of active X-bridges is greatest (maximal thick/thin filament overlap without interference)

Question 27

when is there no tension in muscle?

Answer 27

thick filament is completely compressed, or there is no thin-thick filament overlap

Question 28

when is there slightly less tension in muscle?

Answer 28

thin filament interference, thick filaments hit the z-line, or intermediate thick/thin filament overlap

Question 29

myostatin gene

Answer 29

controls muscle fiber growth

-if inhibited, then causes uncontrolled muscle hypertrophy b/c satellite cell activation is increased