Skeletal Muscle Physiology

Hello All,

Here's another batch of questions.  This time they are regarding the skeletal muscles:

There have been a lot of email issues today, so I hope I have addressed as many of your questions as possible today.  There will undoubtedly be more tomorrow and by the end of the weekend so there will be additional postings as we clear up those confusions as well.  

NOTE however, that regarding your concerns and questions about the length-tension and force-velocity relationships, please see the video blogs to see if they clarify your confusions regarding these relationships.  If they do not, please comment on those blogs regarding your additional confusions and I will attempt to address clarity on those issues there.  I am omitting the questions that I have already received on this subject on this blog post as those two postings will hopefully help clarify many of those concerns.

1.  Is the DHP a Ca channel and also the Ryanidine Receptor a separate Ca channel?

Or are they both parts of 1 channel

Do both of them cause release of Ca from the SR? or does DHP cause Ca to be released from somewhere else?

 

DHP receptor and the Ryanodine receptor are different proteins.  The DHP receptor is the same thing as the L-type Ca2+ channel and is a voltage-gated Ca2+ channel and is located on the sarcolemma membrane within the T-tubule.  The ryanodine receptor is a ligand-gated Ca2+ channel that is located on the membrane of the sarcoplasmic reticulum.  The ligand that activates it in skeletal muscles IS the DHP receptor, but in both the smooth and cardiac system the ligand is Ca2+ itself.  The do, indeed, together cause the release of Ca2+ from the sarcoplasmic reticulum, but the DHP receptor could allow for Ca2+ to come into the cell through extracellular stores as you will see it does in cardiac muscle cells.

2.  If DHP receptor is permeable to Calcium (because it is a voltage gated calcium channel) then where does the sodium ions that generated the action potential at the NMJ go??? 

 

The sodium ions that enter into the motor endplate of the muscle cell through the nAChR initiate the action potential to occur on the sarcolemma of the muscle cell.  Those ions are shuttled back across the membrane by the Na/K ATPase pump just like in the neuron after the AP has finished.  The DHP receptor, in contrast, is located within the T-tubules of the sarcolemma and allow for activation of the Ryanodine receptor and the increase in intracellular Ca2+ concentration initiating contraction.

 

3.  Practice question says:  When skeletal muscle is in its resting state, myosin cross-bridges are directly prevented from binding to actin molecules by which protein?

A.Calmodulin

B.Troponin

C.Tropomyosin

D.Titin

E.Phospholamban

 

tropomyosin clearly covers the binding sites but the ans key says it is titan

help?? 

If the correct answer indicates Titin, it is miss-keyed.  Indeed, tropomyosin directly covers the myosin binding sites on actin.  Remember, however, that troponin is the molecule that keeps tropomyosin in place and without troponin (like in smooth muscles), the tropomyosin does not block the myosin binding sites.

4.  On slide 42 of yesterdays lecture, bullet point #4, is that refering to Ca induced Ca channels?

5.  5.  When comparing the contractile responses in smooth and skeletal muscle, which of the following is most different?

            A.  The source of activator calcium

            B.  The role of calcium in initiating contraction

            C.  The mechanism of force generation

            D.  The source of energy used during contraction

            E.  The nature of the contractile proteins 

I'm having trouble understanding why B is the right answer. The way it seems to me is that the role of calcium in initiating contraction isn't very different (aside from the influence of extracellular Ca in smooth muscle). If calcium is present in high enough concentration you will have contraction in both types of muscles. I think how, or the mechanism of how it occurs, use of different receptors, use of latch bridges, calmodulin etc is very different between the two but not necessarily what calcium does. The way i understand it is that Calciums role is to bind and cause a contraction, its everything else that's different (the how aka mechanism). Any help trying to figure this out or correct my logic would be greatly appreciated, thank you. 

 

In fact your understanding of the differences is exactly what that answer choice is stating.  In skeletal muscles Ca2+ binds directly to troponin initiating cross-bridge cycling to occur while in smooth muscles Ca2+ binds to calmodulin which as a complex is responsible for initiating contraction.  I understand your confusion, but that was indeed what that answer choice was indicating.

6. Regarding #13 on the study quiz:  I understand why E is correct, but would A be correct if the world myoplasm was replaced with the word sarcoplasm?

 

13.  Repetitive stimulation of a skeletal muscle fiber will cause an increase in contractile strength because repetitive stimulation causes an increase in what?

  A.  The total duration of cross-bridge cycling

  B.  The concentration of calcium in the myoplasm

  C.  The magnitude of the end-plate potential

  D.  The number of muscle myofibrils generating tension

  E.  The velocity of muscle contraction

 

Yes, exactly!

 

7.  The Ach binds to receptors on the sarcolema to create an AP but how does the AP move through the sarcolem and into the T-tubule system.  Is the AP propagation into T-Tubules but the same method within the neurons? That being via voltage-gated Na+ channels?

 

Remember that action potentials are movement of ions across a membrane allowing for the propagation of electrical activity along a membrane.  Therefore, the AP propagates along the muscle plasma membrane (sarcolemma) just like it did along the neuronal membrane (axon).  As I mentioned the AP in the skeletal muscle is virtually identical to that of the neuron and is propagated by voltage-gated Na+ and voltage-gated K+ channels.  Those channels are located on the membranes of the T-tubules as well allowing for the propagation of those changes in membrane potential within that area as well.  It is there that the DHP receptors are located.

 

8.  I was doing some practice problems and it says that the temporal summation in a dendrite will reduced if the membrane resistance decreases. I thought it would be reduced if there was higher resistance in the membrane? Can you please explain to me what is the concept behind that? 

 

Remember that a dendrite is the part of the neuronal cell where the graded potentials occur and need to move through the dendrites into the cell body to summate and bring the membrane potential at the axon hillock to threshold.  Therefore, the movement of charges within the dendrites is not a 'given' which is the movement of charges within an axon.  In a dendrite charges want to be 'pushed' towards the cell body to b e summated.  Therefore the decrease in membrane resistance indicates that there is a bigger space for charges to dissipate within the dendrites decreasing the likelihood that the charges will get to the axon hillock.  In an axon, reduced membrane resistance will increase propagation velocity, but the opposite is true within the dendrite.

 

9.  To clarify, those Na+ channels at the postsynaptic membranes are NOT voltage-gated, correct?

 

Post-synaptic membrane receptors are not typically only permeable to Na+.  There are a number of post-synaptic receptors that are mixed-cationic receptors that are permeable to both Na+ and K+ and some are also permeable to Ca2+.  These receptors (ex. nAChR) are ligand-gated NOT voltage-gated.

10.  A question says that T-tubule can carry repolarization to muscle fiber interior, what does that mean?

The T-tubules are sarcolemma membranes that continue from the outside of the cell into the inside of the cell.  Similar to Dr. Yin's balloon analogy, if you poke your finger into a balloon, the balloon itself continues with your finger into the inside.  Just as the depolarization of the action potential can propagate into the interior of the skeletal muscle cell by traveling along this invagination of membrane, so too, therefore would the second part of the action potential, which is the repolarization.

11.  How does increase Ca2+/Na+ exchanger activity shorter duration of skeletal muscle contraction?

 

Na/Ca exchanger is a secondary active transporter that transports Na+ with its concentration gradient (from the outside of the cell towards the inside of the cell) and Ca2+ against its concentration gradient (from inside of the cell towards the extracellular space).  This removal of Ca2+ from the sarcoplasm reduces the Ca2+ able to be bound to troponin, thereby not allowing as many cross-bridge cycles to occur and thereby shortening the duration of the skeletal muscle contraction.

 

12.  Why does longer fiber have higher velocity at isotonic contraction than shorter fibers? 

Each of the sarcomeres shorten individually.  Therefore if you have 10 sarcomeres in a row all shortening at the same speed then the whole length of the muscle will shorten faster than if you had 4 sarcomeres in a row shortening.  Each individually would have the same velocity, but as a whole set the speed they can get to a shortened contractile state is faster.

13.  You mentioned in class that increase of ADP+Pi will inhibit cross-bridge cycling, how is that?  Is it because the lack of hydrolysis of ATP will lead to muscles being stuck in the resting state? 

 

There is a biochemical relationship that exists between the myosin head group that is bound to ADP and Pi and the concentration of those molecules surrounding the myosin head group.  Therefore, if you have more ADP and Pi around, then the myosin head group is less-likely to release those molecules slowing down that step in the cross-bridge cycle.  This has been shown, therefore, to lead to muscle fatigue.