KIN 1Y03 Lecture 31: Skeletal Muscle Physiology pt 1 (sliding muscle contraction)

sliding filament mechanism

explains how actin/myosin are moving relative to each other

relaxed muscles in sliding filament mechanism

Relaxed muscles 

• Myofibrils run entire length of muscle

• Only amount of overlap btw myofilament (actin and myosin) changes ⇒ not its length

partially contracted muscle in sliding filament mechanism

Partially contracted muscle 

• Myosin myofilaments stay in center of sarcomere 

• Myosin head attach to the actin adn pull towards the M-line ⇒ actin myofilaments move towards each other) 

• Sarcomere shortens as Z-disks move towards each other 

  • H-zones get small (more overlap) 

  • I-band decreases bc myosin heads are moving towards Z-disks

maximally contracted muscles in sliding filament mechanism

Maximally contracted muscles 

• Actin myofilaments are pulled so close that theyre overlapping @ center of sarcomere 

  • H-zone = GONE (bc no more, only myosin myofilaments) 

  • I-band = GONE / narrow bc myosin heads acc reach Z-disk 

  • A-bands = unchanged (where after time ⇒ length of sarcomere = A-band)

describe the cross-bridge cycle

1. Ca2+ released from SR ⇒ induces contractions of a muscle 

   1. Ca2+ binds to troponin → changes shape of troponin → moves tropomyosin off active site on actin → exposes active site to myosin → myosin attaches onto actin 

      1. Troponin is held over active sites on actin myofilaments

      2. When Ca2+ binds to tropin 

   2. Active myosin heads (w stored energy (from breakdown of ATP) in upright position) 

      1. Has myosin ATPase: hydrolyzes ATP to form ADP + inorganic Ⓟ (gets bound to myosin heads) 

2. Myosin heads bind to actin, forming cross-bridges and Ⓟ is released from the myosin head, but ADP is still bound to the head of myosin myofilament 

• After formation ⇒ energy in head is used to create “power stroke”: when myosin head moves towards M-line ⇒ ∴ pulls the actin myofilament too  

  • ∴ ADP is released 
    

If NO ATP ⇒ rigor mortis: when myosin heads cant detach from actin

• ⤷ occurs in dead people bc their muslces will release a lot of Ca2+ ⇒ myosin binds to actin ⇒ but theyre dead so no ATP ⇒ ∴ no ATP to bind onto myosin head and cannot detect from actin 

3. Myosin cross-bridges rotate towards center of sarcomere (power stroke) and ADP detaches 

   1. Results in myosin head still bound onto myosin myofilament ⇒ to release myosin (needs ATP) 

4. As myosin heads bind ATP ⇒ the cross-bridge detacts from actin 

5. The ATPase on myosin head hydrolyzes ATP to reform ADP + inorganic Ⓟ ⇒ reoriented and energized 

6. Gets ready to bind again to actin, but now, will bind to region of actin thats closer to Z-disks bc we’ve pulled it towards M-line & we want to grab it even closer to the Z-disks

rigor mortis

when no ATP —> so myosin heads cannot detach from actin

⤷ occurs in dead people bc their muslces will release a lot of Ca2+ ⇒ myosin binds to actin ⇒ but theyre dead so no ATP ⇒ ∴ no ATP to bind onto myosin head and cannot detect from actin 

what is necessary for the cross-bridge cycle to continue

ATP available and high levels of calcium in sarcoplasm

resting membrane potential in skeletal muscles

• Resting membrane potential → higher in muscles (more # of K+ leak channels) 

  • ⤷ ∴ greater difference btw inside/outside of sacrolemma 

• ↑ K+ inside cell, ↑ Na+ outside cell 

• Depolarization → will cause muscle action potential (MAP)

whats the neurotransmitter in synaptic vesicles in NMJ

ALWAYS acetylcholin (ACh)

motor end plate

portion of sarcolemma where we have ACh-ligand gated ion channels

steps of NMJ

An action potential arrives at the presynaptic terminal causing voltage gated Ca2+ channels to open ^^ increases Ca2+ permeability of the presynaptic terminal

Ca2+ enters the presynaptic terminal and initiates the release of ACh from synaptic vesicle in the presynaptic terminal

Diffusion of ACh across the synaptic cleft and binding of ACh to ACh receptors on the postsynaptic muscle fiber membrane causes an increase in the permeability of ligand-gated Na+ channels

Increase in Na+ permeability result in depolarization of the postsynaptic membrane ^^ once threshold has been reached a postsynaptic AP result

ACh is rapidly broken down in the synaptic cleft by acetylcholinesterase to acetic acid and choline NMJ ū occur @ center of muscle fiber  ⤷ where AP moves in many DIR (wants to go entire length of sarcolemma)  ⤷ ∴ moves away from NMJ towards either end of muscle fibers and wraps around muscles fiber sarcolemma + move thru T-tubule

The choline is reabsorbed by the presynaptic terminal and combined w Acetyl-CoA to form more ACh (and CoA), which enter synaptic vesicles

Acetic acid is taken up by many cells types

difference between muscle and nervous system neurons

• Always ACh released 

• Always excitatory (depolarization) 

• Has voltage-gated channels that are very close to ligand-gated change on sarcolemma 

• AP move in 𝓂 diff DIR (but always away from NMJ) 

excitation-contraction coupling

Before the cross-bridge cycling process occurs 

Triad: 

• Forms @ regular repeating intervals along length of muscle fibers 

• Occurs in regions where actin and myosin overlaps 

• 2 triads per sarcomere (bc there's 2 regions where actin is able to overlap w myosin) 

At RESTING: 

• Terminal cistern → has alot of Ca2+ stored 

• Ca2+ released channels are closed (and stored in SR) 

  • ⤷ ∴ troponin in resting state (holding tropomyosin over active site on actin) 

At CONTRACTION: 

• Neuron signals MAP ⇒ moves along sarcolemma ⇒ when reached T-tubules ⇒ will drop down inside muscle fibers & move thru T-tubules 

• As membrane potential changes, detected by Ca2+ released channel ⇒ ∴ will open and spill into sarcoplasm ⇒ diffuse into regions where actin and myosin myofilaments 

  • ⤷ Ca2+ binds onto troponin → shape changes → moves tropomyosin out of way → expose active site → myosin is able to bind onto actin myofilaments 

  • ⤷ ∴ allow cross-bridge cycling to begin 

summary of skeletal muscle contractions

1. An AP travels along an axon membrane to NMJ

2. Voltage-gated Ca2+ channels open adn Ca2+ enters the presynaptic terminal 

3. Acetylcholine is released from synaptic vesicles 

4. Acetylcholine stimulates ligand-gated Na+ channels on the motor end-plate to open 

5. Na+ diffuses into muscle fibers, initiating an AP that travels along sarcolemma and T tubule membrane 

6. AP in the T tubule causes opening of voltage-gated Ca2+ channels in the SR, releasing Ca2+ 

7. On the actin, Ca2+ binds to troponin, which moves tropomyosin and exposes myosin head binding sites 

Start of cross (X)-bridge cycling

8. ATP molecules on myosin heads are broken down to ADP and Ⓟ, which release energy needed to move the myosin heads

9. The heads of the myosin myofilaments bend (power stroke), causing actin to slide past the myosin 

To rid of Ca2+: (release of muscles) 

10. Ca2+ must be taken back up into SR → via SERCA pumps (sacroendoplasm reticulum Ca2+ ATPase) ⇒ which stops muscles from contracting 

11. Ca2+ moves away from tropin ⇒ and tropin moves tropomyosin back over the binding site & blocks myosin from further binding ⇒ muscle relax

3 places ATP is needed in muscles

• Re-establish resting membrane potential (sodium-potassium ATPase in sacrolemma) 

• Myosin heads to detach from actin and create stored energy to undergo another power stroke on the head of myosin 

• ATPase in SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+ ATPase)