Exam 2- Skeletal Muscle Physiology

Question 1

what are the 3 types of muscle

Answer 1

1- skeletal muscle (striated): attached to skeleton/bone
- responsible for general motor movement

2- smooth muscle: associated with body organs (viscera): blood vessels, GI tract, reproductive tract, glands

3- cardiac muscle: heart
- modified form of skeletal, similar striated patterns, but significantly diff patterns in organization and function

Question 2

describe the structural components of skeletal muscle

Answer 2

• horizontal patterns interrupted by vertical bands
  - horizontal are myofilaments- thick & thin filaments (thick= myosin & thin= actin)
  - vertical lines are the z-lines
  - everything in between 2 successive z lines is the sarcomere
• actin filaments are connected to the z line on each side of the sarcomere, but they are discontinuous in the center of sarcomere
• H zone is the space between 2 actin filaments in a sarcomere
• myosin thick filaments are concentrated in middle of sarcomere, not directly connected to z line
• in 2 adjacent sarcomeres, gap b/w myosin filaments called I band
• myosin filament itself is called the A band

Question 3

what is the basic unit of a muscle cell

Answer 3

sarcomere

Question 4

the myosin thick filament is called the __ band

Answer 4

A

Question 5

describe the I and A bands of sarcomere

Answer 5

I stands for “isotropic”- this allows light to pass through (I band is the gap between myosin filaments, across 2 sarcomeres)

A band called “anisotropic”, does not allow light to pass through (A band is myosin filaments)

Question 6

how many actin surround 1 myosin

Answer 6

6 actin surround every 1 myosin (always 6:1 ratio)

Question 7

what are the molecular building blocks that make up the sarcomere

Answer 7

myofilaments

“myo” means muscle

Question 8

define sarcomere

Answer 8

all myofilaments between successive z-lines

Question 9

describe the 2 places in sarcomere that myosin is anchored directly & indirectly

Answer 9

myosin anchored in middle of sarcomere to the M-line by myomesin

anchored indirectly to either side of Z-line by large spring-like protein called titin

Question 10

describe how actin extends in the sarcomere and what proteins allow this

Answer 10

actin filaments start at Z-line, add more and more beads and lengthen it to the center, protein called tropomodulin caps the leading edge and keeps the beads from dissociating

at the trailing end is CapZ, which keeps the beads from dissociating at the Z-line

Question 11

myosin is anchored to M-line by ___

actin is anchored to Z-line by ___

Answer 11

myomesin

alpha-actinin

Question 12

describe the difference b/w myofibrils and myofiber

Answer 12

(myofilaments make up sarcomere)

• if myofilaments laid end to end, make up myofibril (long chain of sarcomeres laid end to end)
• myofiber is a muscle cell- a long cell made of many myofibrils arranged in parallel, held together by muscle membrane
  • muscle cells are kinda like cables, each myofibril is one strand of cable (the more myofibrils you can pack in, the stronger the muscle cell will be)

Question 13

list the arrangement of organization of skeletal muscle

Answer 13

myofilaments –>
sarcomere —>
myofibril –>
myofiber –>
muscle

Question 14

there is more to muscle than just myofilaments…what surrounds myofilaments?describe

Answer 14

inside the muscle cell and wrapped around the myofibrils is an internal set of membranes called the sarcoplasmic reticulum (SR)- flimsy membrane that wraps itself around each of the myofibers (2 components of SR: lateral sac & fenestrated collar)

Question 15

describe the 2 components of SR

Answer 15

1- the lateral sac (terminal cisternae)- associated with the z-line of the sarcomere

2- fenestrated collar- in between the lateral sacs is flimsy membrane to hold everything together

lateral sac associated with T-tubule, T-tubule is an invagination of the muscle membrane itself that goes deep into the muscle cell

Question 16

describe the 2 components of SR

Answer 16

1- the lateral sac (terminal cisternae)- associated with the z-line of the sarcomere

2- fenestrated collar- in between the lateral sacs is flimsy membrane to hold everything together

lateral sac associated with T-tubule, T-tubule is an invagination of the muscle membrane itself that goes deep into the muscle cell
- on either side of T-tubule is a lateral sac (this T-tubule and 2 lateral sacs forms a structure called a triad)

Question 17

what is the function of the lateral sac of the SR?

Answer 17

it is an internal storage site for calcium

• calcium gets in lateral sac by SERCA (sarcoplasmic endoplasmic reticulum calcium ATPase)- pumps calcium into lateral sac of SR
• inside lateral sac is another protein called calsequestrin, a calcium binding protein- 1 molecule of calsequestrin can bind 43 molecules of calcium (high volume, low affinity- binds calcium loosely)

Question 18

describe the mechanism of muscle contraction (which bands/filaments/zones) contract

Answer 18

when a muscle contracts, the sarcomere shortens

• as sarcomere shortens, the H-zone and the I-band get smaller and sometimes completely disappear
• but the length of the A-band and then actin thin filament does not change
• sarcomere gets shorter, but filaments themselves are not contracting –> sliding filament hypothesis (muscle contraction is due to the active inward sliding of the thin filament over the surface of the thick filament towards the center of the sarcomere)

Question 19

sliding filament hypothesis is based off the molecule interaction b/w ___ and ___

Answer 19

actin and myosin

Question 20

describe structure of actin

Answer 20

actin is a polymer of individual beads, form long filaments- 2 that wrap together in helical fashion
- each individual bead is globular protein called G-actin (globular actin)
- long filament called F-actin (filamentous actin)
- all along the actin filament, the individual G-actin molecules have binding sites that allow it to attach to myosin (actin pulled across surface of myosin, so has to connect somehow)

2 other proteins in actin polymer:
1- tropomyosin: wraps itself around the surface of the filamentous actin, by doing this, it covers up/masks the binding sites all along F-actin polymer (at rest- actin binding sites are masked and cannot bind w myosin)
2- troponin (globular protein all along tropomyosin), specifically troponin C (c for calcium)- a calcium binding protein
- at rest, actin associated with troponin-tropomyosin complex which sites on surface of actin polymer, inhibiting binding sites of myosin

Question 21

describe the structure of myosin

Answer 21

myosin has a head and a tail

• the tail called the light meromyosin (LMM)- makes up the central core of the myosin filament- whole bunch of tails wound together, makes the core of the myosin molecule
• the head called heavy meromyosin (HMM)- the physiologically important components are found in the myosin head
  • myosin head has complementary binding sites for actin, also has myosin ATPase (needs ATP for muscle contraction)
  • regulatory and essential light chains are on the heavy meromyosin head (regulatory light chain is another calcium binding protein, when binds calcium –> activates myosin ATPase)

Question 22

where are the physiologically important components of myosin found

Answer 22

in myosin head (HMM)

Question 23

after AP is transmitted from motor neuron to muscle membrane and sodium channel of nicotinic receptor depolarizes membrane to threshold, what happens?

Answer 23

starts AP on muscle membrane –> once AP generated on muscle membrane, starts process called excitation-contraction coupling (cause & effect: once AP generated on muscle membrane, will cause cell to contract, the 2 processes are coupled, AP will always lead to contraction)

• AP travels along muscle membrane and then reaches T-tubules (transverse tubules)- T-tubules are deep infoldings of membrane, go deep into center of muscle cell
  
  • muscle cells are big, large diameter, so T-tubules go to center of thick muscle cell (when AP hits T-tubule, travels down T-tubule to center of muscle) –> allows entire muscle to be stimulated simultaneously

Question 24

membrane of T-tubule is very closely associated with membrane of the lateral sac of the SR…describe receptors

Answer 24

there’s a pair of receptors (one in t-tubule and on in lateral sac of SR)
- t-tubule receptor called DHP receptor (gets name from dihydropyridine- pharm agent)
- lateral sac receptor called ryanodine receptor (pharm agent)

these 2 receptors are physically linked - as AP sweeps down membrane of T-tubule, hits DHP receptor –> energy from AP causes DHP receptor to change shape –> this causes change in shape of ryanodine receptor (ryanodine receptor forms a calcium channel in the SR lateral sac membrane) –> this calcium channel opens up when ryanodine activated

Question 25

what kind of channel is the calcium channel of the ryanodine receptor

Answer 25

mechanically-gated channel
activated b/c of change in shape of receptor

Question 26

what protein is associated with the inside of the ryanodine receptor and what does it do

Answer 26

calsequestrin (calcium binding protein, binds 43 calciums loosely)- as soon as ryanodine calcium channel opens, calsequestrin gives up its calcium, flows out of SR and into sarcomere

Question 27

after ryanodine receptor is activated and calsequestrin gives up its calcium which flows into sarcomere, calcium has 2 functions in sarcomere:

Answer 27

1- calcium binds to troponin C of troponin-tropomyosin complex –> this alters conformation of the complex –> complex becomes buried deep into grooves of F-actin helix –> exposes binding sites all along actin polymer

2- simultaneously, calcium binds to regulatory light chain of myosin head –> changes conformation of myosin head, allows ATP to bind to active site of myosin ATPase –> starts process of powerstroke

Question 28

describe process of muscle contraction- power stroke

Answer 28

calcium floods sarcomere and allows ATP to bind to myosin head –> ATP split by myosin ATPase and energy is used to pull back myosin head, bringing myosin close to actin, as soon as myosin head pulled back, active sites on myosin come into contact with binding sites on actin –> actin and myosin form cross-bridges (link/hook together) –> cross-bridge formation triggers release of stored mechanical energy, myosin head rotates inward (power stroke), pulling actin into surface toward the center –> new conformation causes release of ADP and Pi, myosin head disengages from actin, myosin head back into normal conformation, waiting for another ATP to bind

Question 29

in the power stroke muscle contraction, converting __ energy of ATP to __ energy, pulling myosin head back

Answer 29

chemical
mechanical

Question 30

as long as you have __ and __, can get another rest and powerstroke (each powerstroke shortens the sarcomere and contracts the muscle a little bit more)

Answer 30

ATP and calcium

Question 31

how does a muscle relax? relaxation starts with…

Answer 31

a 2-step process that clears calcium from the sarcomere

1- soluble protein in sarcomere called parvalbumin- another high volume, low affinity calcium-binding protein (will bind a lot of Ca quickly, this drops the level of Ca in sarcomere very quickly –> when drop levels of calcium, it comess off other calcium binding proteins (troponin) by diffusion –> troponin-tropomyosin complex goes back to original position and masks the actin binding site –> no more cross-bridge formation or contraction
- at same time, calcium comes off myosin head (myosin ATPase goes back to inactivated state), myosin head goes back to its resting position

2- transfer of calcium from parvalbumin to the SERCA, pumps calcium back into the inside of lateral sac of SR (pump has much higher affinity for Ca, why its able to pull Ca off parvalbumin)

Question 32

what is a secondary way to get calcium out of sarcomere for muscle relaxation?

Answer 32

sodium pump –> pumping sodium out of sarcomere (sets up inward sodium gradient- this drives a sodium-calcium exchange protein), sodium in and calcium out

Question 33

once cross-bridges are broken, muscles relax to normal length, the mechanism involve is due to what?

Answer 33

series elastic elements/components (sarcolemma, z-line, endomysium, perimysium, epimysium, ligaments, tendons)

• series elastic elements are cellular molecular components of muscle that are stretching/elastic, but not contractile (myofilaments are contractile)
• non-contractile, but elastic- they stretch/compress during contraction and spring back to their normal length during relaxation