What does G-actin spontaneously do?
G-actin spontaneously polymerizes into F-actin.
What forms the backbone of the thick filament?
Large portions of heavy chains interact with one another to form the backbone of the thick filament.
What parts of the globular proteins form the crossbridges?
Myosin heads protrude from the backbone of the thick filament to form crossbridges.
Where are actin and myosin found?
Actin and myosin are in every muscle cell. Each protein monomer exists in multiple isoforms in different proportions, depending on the type and stage.
What is the structural arrangement of the sarcomere?
Z line - thin filament - thick filament - thin filament - Z line.
At the cellular level, what happens when striated muscles contract?
Crossbridges from the thick filaments attach to specific regions on the actin molecules. The crossbridge heads change angles, so the thick and thin filaments slide over one another. The crossbridges release and are ready to attach to a different actin molecule.
Could you summarize that or something?
When striated muscle contracts, the Z lines move closer to one another. The thick and think filaments sliding over one another do not change length.
Describe crossbridge cycling in four easy-ish steps.
Myosin crossbridge attaches to actin A conformational change of the myosin crossbridge causes sliding of the thick and thin filaments with the dissociation of ADP and Pi ATP binds to the crossbridge causing the crossbridge to dissociate from the actin ATP splits changes the crossbridge to its original state
What is rigor?
Crossbridges remain attached but do not cycle because there is no ATP.
What does the troponin-tropomyosin complex do?
It interferes with the interaction of crossbridges with actin.
So what interferes with the interference of the trop-trop complex with crossbridges and actin?
Calcium binds with the troponin C of the thin filament. Thus the myosin binding site of the actin filament is uncovered.
Where does this Ca2+ come from?
Ca2+ is stored in the terminal cisternae of the sarcoplasmic reticulum, which are well developed in skeletal muscle and less so in cardiac muscle.
How does the Ca2+ get out of the terminal cisternae?
APs propogate into the the interior of the cell via T tubules of the membrane and release Ca2+, VGCC open and it moves into the cytoplasm down its concentration gradient.
How much Ca2+ enters the cell during the AP?
In skeletal muscle, there is a minimal influx of extracellular Ca2+. In cardiac muscle, there is a significant influx of extracellular Ca2+.
What is the tie between Ca2+ and muscle relaxation?
There is reuptake of the Ca2+ by the SR using Calcium ATPase to the terminal cisternae. Then the muscle can relax, becuase the myosin binding site has been covered up again.
Can skeletal muscle contract in a Ca2+-free soln?
Can cardiac muscle contract in a Ca2+-free soln?
No. Extracellular Ca2+ influx is critical for cardiac muscle contraction.
Is the AP duration longer in the skeletal muscle or cardiac muscle?
Cardiac muscle. VGCC are open longer, too.
Where does the E for muscle contraction come from?
ATP is hydrolyzed by myosin.
So, myosin is an ATPase?
Yes, though it is slow. Adding actin accelerates the process.
How is Ca2+ removed from the cytoplasm in skeletal muscle?
Nearly all the Ca2+ is taken up by longitudinal SR.
How is Ca2+ removed from the cytoplasm of cardiac muscle?
Significant amounts of Ca2+ are removed via a sodium-coupled calcium exchange pump. The pump is an example of secondary active transport.
Pretend you delivered electric pulses to a muscle and nothing happened. Why did you fail to elicit a response?
The intensity did not reach threshold.
You deliver more intense shocks and elicit a few muscle twitches. Why did these muscle cells twitch and not other ones?
The cells that twitch first are the most excitable cells.
You deliver shocks of increasing intensity. As intensity increases, contractile force increases. Eventually you are increasing the intensity but don't see an increase in force. Why did you fail this time?
At a certain point you have used a supramaximal pulse and can't recruit any more muscle cells.
Recruitment occurs in skeletal muscle, but not cardiac muscle. What's up with that?
Skeletal muscles cells are not coupled electrically to other cells, cardic muscle cells are. So when the most sensitive cardiac cell reaches threshold, excitation spreads to the other cells.
What happens if you deliver a second supramaximal pulse before the muscle relaxes from the first one?
The pulses are summated and the second contraction will be larger.
What is a tetanic contraction?
A pulse frequency is so high that muscle response to a single pulse cannot be detected. A smoothly shaped contraction to a maximum force is obtained.
What is the relationship of Ca2+ to an AP during tetanus?
Each pulse elicits an AP, but Ca2+ levels do not fall between APs.
What is going on with crossbridges during tetany?
As soon as one crossbridge is broken, one is made.
What does a length-passive force diagram illustrate?
It shows that the resting force remains at almost imperceptible levels over initial changes in length, the force increases exponentially with further stretch. Passive force is ALWAYS present because it is due to the structure.
What does a length-total force diagram illustrate?
It shows the peak force during tetanus at each muscle length.
What is optimal length?
The length of a muscle that produces maximal active force and no tension from passive force. Active force is produced by crossbridge cycling.
What is length-passive force relationship affected by on a cellular level?
The relationship is due to the elastic behavior of the cell membranes and of the connective tissue between muscle cells.
At Lo, what is going on with actin and myosin?
The thick and thin filaments overlap so almost every myosin crossbridge is capable of interacting with an active site on actin.
What is going on with crossbridge interaction at different lengths?
At Lo, you have the maximum number of crossbridges interacting with actin. When you stretch the muscle, the overlap of filaments shifts so there is less interaction. If you stretch the muscle far enough, there is no overlap and no interaction so no active force.
Stretching a muscle reduces overlap. But what about shortening the muscle? Would the overlap be the same?
When a muscle cell shortens, the volume is the same, so what changes in the cell is the diameter. Now the filaments are further apart laterally, and the strength of the crossbridge decreases.
In summary, what are the three influences of skeletal muscle contraction under isometric conditions?
1) the # of cells stimulated. 2) the frequency of stimulation 3) the length of the muscle cells before stimulation
On to isotonic contraction. What is preload?
Preload is the stretch a muscle feels before it contracts. It is aware of preload.
What is a muscle not aware of before contraction?
Afterload. Does you muscle know if you just grabbed a 5 lbs dumbell or a 50 lbs dumbell? No it does not.
Your muscle has managed to produce more force than the afterload produces. Congratulations. What happens to the muscle?
The muscle shortens and the initial velocity of shortening can be recorded.
What does a force-velocity relationship describe?
The initial velocity of a muscle for different afterloads.
What happens to the initial velocity of muscle shortening if you increase afterload?
As afterload increases, initial velocity decreases.
Pretend you test a skeletal muscle using different preloads, but the afterload always equals 0 force. What is the initial velocity?
With no afterload, the muscle achieves maximal velocity. For every preload, that maximal velocity is always the same for that muscle.
Each muscle has a different Vmax. Why?
Vmax is a function of myosin, which has different isoforms (variants of the same enzyme).The different isoforms have different ATPase activities.
In skeletal muscle, Lo has no passive force. What about cardiac muscle?
Passive force is 20% of the total force in cardiac muscle at Lo.
What happens to cardiac muscle beyond Lo?
The heart's ability to pump decreases as it fills more and more. If it was a cartoon heart, it would eventually explode.
What is the difference of AP duration regarding cardiac and skeletal muscle?
Cardiac AP = 300 msec. Skeletal AP = 1-3 msec.
They have different AP durations. So?
So Ca2+ has more time to interact with troponin C in cardiac muscle, more time for tension development with single AP, and no tetany.
Length-tension relationship of cardiac is not due to mechanical overlap. What does it depend on?
Length-tension depends on the affinity of troponin C for Ca2+. As the length changes, affinity changes.
As affinity for Ca2+ increases, what happens to available Ca2+?
As troponin C's affinity for Ca2+ increases, you don't need as much available Ca2+ for half of troponin C to be filled with Ca2+.
If contractility of cardiac muscle is decreased, what happens to Vmax?
Vmax is lower in cardiac muscle that is less contractile than control tissue.
In the skeletal muscle, force changes with length. What is analogous with cardiac muscle?
A change in volume changes pressure.
Why does passive force kick in before Lo in cardiac muscle?
Passive force kicks in so you don't need as much active force to prevent stretching beyond Lo, which increases Volume.
What 3 things are high in FT fibers and low in ST fibers?
Myosin ATPase, glycolytic metabolsim, Vmax.
What 3 things are high in ST fibers and low in FT fibers?
Oxidative metabolism, mitochondrial content, myoglobin content.
What is the ultimate ST fiber?
Does cardiac muscle prefer glycose or lactate?
What can the body use lactate for?
What does rapid glycolysis produce?
2 ATP + lactate
What are sources of ATP for muscle cells to use?
Stored ATP, creatine phosphate, glycolysis, oxidative phosphorylation, type IIa fibers.
If your muscle is exhausted, is ATP depleted?
No, creatine is.