Flashcards in Muslce Physiology Deck (32):
In skeletal muscle, does the AP precede the peak of the calcium transient?
YES, and as the calcium decreases from its maximum, we will see an increase in muscle tension due to the actin and myosin interacting.
What does the architecture look like around the Transverse (T) tubules of skeletal muscle?
You have triads of a T tubule (part of the sarcolemma membrane), abutted on either side by sarcoplasmic reticulum (called terminal cisternae).
Does cardiac muscle make junctions with the T tubule?
NO. It does form some diads however.
How does contraction coupling differ in cardiac muscle?
It involves calcium induced calcium release, opposed to skeletal muscle which is voltage sensitive sodium induced (via DHP receptor on T tubule) calcium release (via ryanodine receptor, which itself is a calcium channel of the SR).
How does cardiac electrical-contraction coupling of calcium induced calcium release work in cardiac muscle?
the initial calcium enters from the extracellular space (T tubule) through a voltage-sensitive L-type calcium channel. Some of the Ca++ binds to the ryanodine receptors on the SR causing these channels to open, letting more Ca++ into the cell.
**How is the Ca++ taken back up in cardiac muscle after contraction?
transmembrane pumps called calcium-ATPases, interact with phospholamban (which in the inactivated state, aka during muscle contraction, binds to the Ca++ pump to decrease the rate of Ca++ reuptake, but in the activated phosphorylated state, aka to let the muscle relax, allows the pumps to operate) to pump Ca++ against its gradient to remove it.
*Think about phospholamban like an idling car engine. When you step on the gas pedal (aka removing the inhibition of the engine) the engine speeds up. In the same way, when you phosphorylate phospholamban at the end of muscle contraction, the Ca++-ATPase can reuptake calcium for the muscle to relax.
What will beta-adrenergics do to the Ca++-ATPase?
speed up this pump, allowing it to relax more quickly to pump again more quickly. It also loads more Ca++ into the SR for the next contraction, thus increasing the release of Ca++ for a stronger contraction.
How does contraction coupling occur in cardiac muscle following calcium release?
Ca++ binds to troponin-C, removing the blocking action of tropomyosin on the actin filament. This opens the myosin binding sites for the myosin heads to bind to.
What is important about the isoforms of troponin?
there is troponin I, C, and T. These are clinically important because during an MI, these will show up in the blood serum.
To what is force proportional in the cardiac muscle system?
the number of myosin heads that can interact with the actin, regulated by the amount of calcium allowed into the system.
Does skeletal or cardiac muscle have a steeper logarithmic relation of tension to calcium?
skeletal muscle. In other words, fast skeletal muscle goes from 0 to 100% contraction over a narrower range of Ca++). This is suited for all or nothing control.
Cardiac muscle on the other hand is sensitive to sarcomere spacing (meaning the more stretched it is, the greater the force of contraction for a given amount of Ca++). This is why the contractility of the heart matches the volume that enters it.
What are the accessory proteins of the sarcomere and what do they do?
nebulin and titin, which help to maintain the lattice work of the sarcomere structure and contribute to the series and parallel elasticities of the structure.
** How does the biochemistry of actin and myosin interaction cause contraction?
The two-headed myosin head (the two work independently from one another, so we will look at the one closest to the actin filament) has an ATP binding pocket, which will hydrolyze ATP upon its binding.
1. Following Ca++ influx, the myosin head with (ADP + Pi) will form a cross bridge with the actin.
2. The gamma Pi will be released from the head (think that it can't hold on to both the actin and Pi at the same time when it binds to the actin, so it drops the Pi; like pulling the pin of a stretched spring). Loss of this gamma Pi= CONTRACTION of the myosin head (moving the actin filament). This is the slowest step and only NONREVERSIBLE reaction.
3. ADP will be released soon after contraction (Note the head is still bound to the actin when this happens).
4. ATP can then bind to the empty myosin ATP pocket, causing the myosin head to dissociate from the actin filament (loses its affinity for actin).
5. The ATP will hydrolyze to ADP + Pi, causing the head to reset/recock (storing the energy from the hydrolysis; like loading a spring to be released) in anticipation for more calcium to enter.
Are the myosin heads at different states at any given time throughout contraction?
What do the myosin heads in the post-power stroke do to those in the pre-power stroke?
impede them, because contraction cannot occur until those post-power stroke heads disassociate (via ATP binding). This occurs more at faster rates of contraction (i.e. faster heart rate or skeletal muscle contractions). This helps to explain why people cannot keep running faster and faster.
Why can't people keep running faster and faster?
because the POST-power stroke heads in the sarcomere heads are unable to detach quickly enough for the PRE-power stroke heads to propel them forward.
What does the force-velocity relationship show?
As you increase load, the velocity of shortening decreases until you reach an isometric contraction, at which point if you continue to increase the load, the sarcomeres will start to lengthen.
** What does a lowered pH (increase in H+) do to muscle contraction?
inhibits attachment and force, and SLOWS velocity because the ATP cannot be hydrolyzed due to too much H+, which is a product of hydrolysis (ATP + H2O ADP + Pi + H+).
** What does elevated Pi do to muscle contraction?
inhibits attachment and force (remember because if you can't remove the Pi (the pin of the spring) you can't attach and contract the spring), but doesn't change velocity (because the heads cannot bind for contraction to occur)
** What does elevated ADP do to muscle contraction?
inhibits DEtachment of myosin head (because if ADP can't leave, it won't allow detachment of myosin head via binding of ATP). This will also SLOW the velocity (because it traps the myosin head in a post power stroke state), and intriguingly will INCREASE isometric force (because the head has gone through its power stroke and is still holding on, so the sarcomere will not lengthen).
** What happens without ATP?
rigor mortis occurs because the myosin heads cannot detach from the myosin binding sites.
How is energy (ATP) disguised when produced by the mitochondria?
via creatine, which binds the gamma phosphate of ATP to creatine to form phosphocreatine (via creatine phosphokinase), and will be used to replenish ATP levels at sarcomeres distal to the mitochondria during muscle contraction. This keeps the levels of ATP high relative to ADP.
This is called the phosphocreatine energy shuttle.
Is phosphocreatine long or short acting?
very short for quick contractions, because it runs out quickly. This is why weight lifters will dope with creatine.
What system kicks in following usage of phosphocreatine?
lactic acid system
What system maintains sustained exercise?
the aerobic system, utilizing FA and glucose to pyruvate for energy production to the TCA (oxidative phosphorylation)
What are the 3 classifications of skeletal muscle fibers?
1. Fast glycolytic= glycolysis for ATP production, strong muscle contractions, but fatigue quickly.
2. Fast oxidative glycoolytic= glycolysis and oxidative phosphorylation (intermediate).
3. Slow Oxidative= oxidative phosphorylation for ATP production, weaker muscle contractions, but do NOT fatigue quickly.
* the type of alpha motor neuron determines the type of muscle fiber.
What type of muscle does cardiac muscle most resemble?
slow oxidative muscle fibers, because it cannot fatigue, and hence the abundance of mitochondria in cardiac tissue.
What is the length-tension curve?
the force that a skeletal muscle can generate depends upon its length when stimulated to contract. This is analogous to Starlings curve in the heart.
** How do tension relationships differ between skeletal and cardiac muscle?
- the total tension (active + passive) of SKELETAL muscle begins to DECREASE for a time period at the length of the active tension's maximum, until the PASSIVE tension increases enough to match the tension of the ACTIVE tension. Hence, it operates at a longer length, which is at its MAX tension).
- for CARDIAC muscle, total tension will NEVER DECREASE, even when the active tension begins to decrease, because the PASSIVE tension increases at a much shorter length. The consequence of this is the more the wall of the heart is stretched, the more it resists being stretched out further (aka the stronger it gets).
Why does cardiac muscle operate at a shorter sarcomere length?
the titin proteins in its structure have fewer repeats and so it's shorter, thus increasing the amount of actin and myosin overlaps :) Note: the actin and myosin are NOT shorter. They are still the same.
What is the biochemical speed limit for contraction?
when there is zero external load. Hence, I can contract with max velocity.