lecture 2 - DESIGN OF SKELETAL MUSCLE

• whole muscle surrounded by epimysium (connective tissue)

• fascicles (group of fibers) surrounded by perimysium

• myofiber surrounded by endomysium (overlays sarcolemma - muscle fiber cell membrane)

  • like saran wrap**

**contractile apparatus consists of parallel cross-striated myofibrils

SLIDING FILAMENT THEORY **myofibrils responsible for contraction

1. Myosin

   • larger (500kd), thick filament

   • features globular heads acting as ATPase (determines rate of contraction)

   • M line in middle of myosin molecule, heads in each side move toward M line (bipolar)

its structure allows it to form filaments with motor heads oriented in opposite directions at each end, enabling it to generate contractile force by pulling on actin filaments simultaneously in opposing directions

2. Actin

   • smaller (42kd) called thin filament

   • 2 intertwined subunits (forms grooves → has troponin and tropomyosin)

   • no ATPase

   • terminates at Z-line (sarcomere)

Z to Z line = 1 sarcomere

H zone gets smaller when contracting

** no inherent directionality when contracting; both sides of sarcomere pull in to middle

** myosin heads cover whole myosin not just top and bottom

• wrapped around actin is Tropomyosin

• associated with tropomyosin is troponin

• troponin consists of 3 subunits

  • TnI - bound to actin - inhibits interaction between actin anf myosin

  • TnT - bound to tropomyosin - anchors troponin complex to actin

  • TnC - bound to calcium - calcium sensor that triggers conformational change

tropomyosin physically blocks the myosin binding sites on actin when calcium levels are low; when calcium levens increase it binds to TnC and triggers a conformational change that moves tropomyosin away, allowing myosin to bind to actin and powerstroke to initiate muscle contraction

**ATP doesn’t do the contraction - it just releases the potential energy PE

***********************short answer??

4 FEATURES OF MUSCLES

exciteability - ability of a muscle to respond to a stimulus

extensibility - muscle's capacity to be stretched or extended without tearing.

elasticity - muscle's ability to return to its original length after being stretched.

contractility -The muscle's ability to shorten and produce force when stimulated.

each myosin surrounded by 6 actin

each actin surrounded by 3 myosin

in space → muscles get weaker bc there’s no gravity

loss of strength not just from atrophy → lose alot more strength than mass

what happens is that stroichiometry changes

• measures 1:5 or 1:2

  • reduces the # of actin-myosin cross-bridges

**tendon connects muscle to bone

fasciculi/fasciculitis - (different fiber types in the fasiculi)

• pull out 1 fasicle

  • pull out a single fiber - striation from myosin and actin

    • pull out 1 myofibril - myofibrils don’t get bigger they just increase in number (fibers get bigger)

sarcomere - smallest functional unit of muscle

contractile protein: myosin, actin

regulatory protein: troponin, tropomyosin

titin

• plays a role in how much force you can produce

• on the end of myosin and binds myosin to Z line - strong anchor fiber

• produces 20-25% of the overall force during??

during contraction:

I band reduced, A band has no change, H zone reduced

******************************************THIS IS ON SHORT ANSWER

SLIDING FILAMENT THEORY OF MUSCLE CONTRACTION

1. nervous system → action potential propagates to SR; calcium released from SR binds to TnC

2. Causes conformational shift that is transmitted to rest of troponin and to tropomyosin

3. tropomyosin buried deeper in groove between 2 strands of actin, then exposing binding (active) sites

4. energized myosin cross bridge head (ADP & Pi bound) binds to exposed actin binding site

5. releases stored energy in crossbridge head and powerstrike occurs pulling actin over myosin

6. during power stroke ADP and Pi released from cross bridge head

   • increase or decrease in affinity depends on the release of Pi from crossbridge head (inc. in affinity when Pi is released)

7. At the end of power stroke, crossbridge head stays attached to actin until a new ATP molecule binds to crossbridge head of myosin breaking acto-myosin complex

8. ATPase of crossbridge head immediately hydrolyzes ATP; leaving crossbridge head in energized position ( snapped back to original position) with ADP and Pi head.

9. Proccess continues (cross bridge cycling) until cytosolic calcium returns to normal and actin binding sites are masked again

In any fiber, cross bridge cycling occurs asynchronously (allows tension to be maintained rather than cycles off and on)

• meaning different myosin heads attach and detach from actin filaments at slightly different times, which allows for continuous tension generation and smooth muscle contraction rather than a jerky on-and-off cycle.

• same speed but not the same time for smooth contraction

ATP provides possibility of power stroke - not power stroke directly

**shortening has no direction

**power stroke happens before release of ADP and Pi

• the two are not released together

• when Pi is still attached → weak binding

• vs strong binding

Rigor Mortis

• can’t get rid of Pi → because there is no new ATP molecule

• the myosin head stays cocked

• ATP is depleted, the cross-links between actin and myosin become irreversible. This results in the muscles remaining permanently contracted,

Role of Ca2+ in contraction

• AP propagates down T-tubule

• the DHP receptor senses a voltage change and signals the ryanodine receptor to release calcium ions from the SR

• SR calcium pump is always on - actively pumping calcium ions into SR

• but it becomes overwhelmed when an AP causes massive release of ca from SR → significant increase in calcium concentration