Cardiovascular Health Research

Hello All,

Here is an interesting article about current cardiovascular research that I thought you all might find interesting.  Shared with me by one of your fellow classmates.  Please feel free to send me other articles as you see them so that we can all see together how what we are learning right now is of use for us and future medical professionals in the future!

http://online.wsj.com/article/SB10001424052702304550004577508733483782646.html?mod=rss_Health

Cardiac Muscles

Let me first start by apologizing for two things:

1.  I am sorry that I covered this material quite fast.  I hope, though, that as entertaining as it may be at half-speed on Mediasite, that will allow you to gather all of the things that I said together.

2.  I am sorry that I went over the 50 minutes.  I know it is NOT FAIR to you at all to do that and I try VERY hard not to, but unfortunately this time it happened.  

Here is a link to an interesting article that one of your classmates sent me.  Looks like there are going to be really cool things coming in the world of cardiovascular medicine that may in fact involve people who are 'heart-dead', but still living: 

http://www.npr.org/2011/06/13/137029208/heart-with-no-beat-offers-hope-of-new-lease-on-life

 

Now, on to your questions.  As I did cover this stuff quite fast there are a few really good questions here that will allow me to clarify things a bit more.  Here's what you have come up with so far:

A couple of questions came up regarding answer choices and how there was the answer choice to one question missing.  Indeed, there was.  Questions with pictures are difficult to put into the notes section, so those got left off and when I was transposing the answer choices I made a mistake.  Here, however is what the correct answers of the MCQs at the end of the lecture should read:

 

Correct Answers:

1.B

2.D

3.D

4.C

5.A

6.B

7.D

8.E

9.D

10.B

11.A

12.B

13.B

14.D

15. E

17.C

18.D

19.C

20.A

21.B

22.E

This may clear up a few of the questions below, but as I believe there may still be some questions, I will give some reasonings for the MCQs questioned below anyways :).

1) I don't know if I'm getting this right but in the skeletal muscle At REST the scarcomeres are arranged at or close to optimal length, but in the heart the sacromeres are at optimal length when the muscle is contracting.

YES!  Because you want to have contraction happen when there is optimal interaction between myosin and actin, and typically contraction happens from approximately 'rest length' in skeletal muscle, the rest length is where there is optimal interaction between myosin and actin.  In the heart, however, prior to each contraction, the heart fills with blood.  Therefore, when the excitation (action potential) and contraction occurs, the muscle fibers themselves are stretched beyond their rest length.  At that stretched length, there needs to be optimal interaction between myosin and actin (close to the peak of the active length-tension relationship), so the rest length of cardiac muscles is shorter than optimal allowing for optimal arrangement to be achieved at a stretched length.

2)  On the last slide of the lecture labelled as muscle cell conduction, a calcium channel is opened at  the phase 1 of the fast-rapid muscle action potential.  The previous slides stated anything about opening of any calcium channel during that phase. I'm confused. I'd appreciate if you could clarify that.

The very last two slides, as I mentioned in lecture, are alternative ways to look at the two types of action potential (slow response and fast response) that occur in the heart.  The last slide does snow that the L-type Ca2+ channel begins to open during the 'notch phase' or phase 1 of the action potential.  This is accurate, but the majority of the movement of ions through this channel occurs after that initial repolarization, and that is what causes the delayed repolarization that looks like a plateau.  L-type Ca2+ channels are voltage-gated and the voltage that initiates their opening is threshold.  They are just slower to open, however, than the Na+ channels, so by the time they are opening the Na+ channels have already opened and are inactivated and one type of K+ channel has begun to open.  Therefore, the timing of the precise movement of Ca2+ is during the notch phase, but really takes off during the plateau phase.

3) for the quizzes that you have posted on the gdrive, I tried to open it by dragging it into another browser but it doesn't work, I must be doing it wrong. can you please show me how do i access them?

As I have said many times the quizzes can ONLY be opened from the actual network G-drive, not remotely.  Here are the instructions I posted:

In the past, students have experienced problems when they try to run the Articulate quizzes from the “Students G-drive Online” connection, so please use the “Ross Net Drive [G drive]” available on campus.  In actuality, you do not need to run this quiz file from the G drive at all, and I recommend that you copy the entire folder onto your desktop or a USB drive and then run the quiz from any common browser (IE, Chrome, Firefox & Safari).  Note:  If you copy the folder off the G drive, be sure to copy the entire folder and not just the quiz – if you don’t have the contents of the entire folder (some application files are hidden) the quiz will not run.  Please email me if you experience any difficulties.  

Go to the folder on the G-drive for the lecture (example: G:\Semester 1\Block 1. Fundamentals 1\Fundamentals.part 1\Membrane Transport Mechanisms Dr. Johannessen(PHYSIO)) and copy the folder within for either the thought questions or practice question onto your desktop or a USB drive (again, copy the ENTIRE folder as there are contents in the folder unseen that MUST BE present to operate the quiz), then open the quiz within a web browser by dragging the quiz file to an open web browser on your computer and the quiz itself should open automatically.  Either of the visible files within the folder should work within a web browser in this manor.

Alternatively, here are instructions that another faculty member posted (as they may be more clear):

1.  DO NOT ATTEMPT TO ACCESS THESE FOLDERS OFF CAMPUS –“Students G-drive Online” will NOT allow you to easily copy the quiz folder and its files (some of which are hidden).

2. ON CAMPUS – USE the “Ross Net Drive [G drive]” utility (you should all have this – if not see IT who will install it for you).

3. Navigate to the lecture folder on the G drive – open it.

4. Copy & paste (or drag and drop) the folders onto your laptop or a USB memory stick. YOU MUST COPY THE FOLDERS – At this point do NOT open them. If you are asked whether you want to copy subfolders or hidden files - click on “Yes”.

5. To use the packages - when you have copied the two folder onto your laptop or memory stick  – open the folder you want to use and simply double click the HTML file or drag it to an open web browser and they will then start. If when the browser starts you get an Adobe Flash security warning click “OK”. The quiz or the electronic glossary will then start.

These materials have been tested on MACs and PCs and will run with Internet Explorer, Firefox, Chrome and Safari. You MUST have “Adobe Flash” installed in order for them to run. Make sure that you have the latest version of Flash – if not - update it from http://www.adobe.com/downloads/.

If you are still having troubles, please come and see me with a USB memory stick and I will give you the folders.  These questions are the SAME QUESTIONS, however, that are posted at the end of the powerpoint lecture, so either way of doing the practice questions is sufficient.

 

4) I am having trouble grasping one thing about the slow response phases.  So during phase 4 the "funny" channels open and subsequently open T-type and L-type channels right? Then phase 0 comes along at which point L type channels are supposed to open. What's going on here? What is different about these L channels that keeps them inactivated during phase 4?

'Funny' channels are voltage-gated channels that open at a hyperpolarized membrane potential, so when the membrane is repolarized by K+ channels, the 'Funny' channels are triggered to open.  This allows for influx of Na+ that slowly depolarizes the membrane.  That slight depolarization causes the voltage-gated T-type Ca2+ channels to be opened.  The influx of Ca2+ through those channels further depolarizes the membrane that brings the membrane close to that of threshold that causes the voltage-gated L-type Ca2+ channels to open, further depolarizing the membrane and initiating phase 0 (the depolarization phase) of the action potential.  There are only one type of L-type Ca2+ channels and they open close to the end of phase 4 and the beginning of phase 0.  I know this was not made extremely clear on the slides and I apologize for that.  It is a cyclic process, however, where the repolarization by K+ channels causes hyperpolarization that opens up the 'funny' channels, causing depolarization opening up the T-type Ca2+ channels, causing depolarization opening up the L-type Ca2+ channels, causing further depolarization the eventually results in repolarization by the K+ channels and the entire process happens all over again. 

Also, one of your fellow students wanted to provide this piece of wisdom for you, I think it is great advice:

In the classroom, I believe a student asked what is causing the actual AP to be generated during the Slow Response. The answer was the funny gated channels and the subsequent T and L type Ca++ channels. What made it easier for me to understand this was by keeping in mind the very nature of these cells. They are rhythmic, repeating a cycle. If you draw the steps in a circle, and keep L type Ca++ channels between step 0 and step 4, I think students will find it much easier visualize the whole process. 

5) The terms Automatic, conducting cells, and pacemaker cells appear to the same thing. Is this correct? 

Pacemaker and automatic cells ARE the same thing and constitute the cells of the SA and AV nodes.  The conducting cells, however, typically constitute the cells of the bundle of His and the purkinjie fibers and (as shown on slide 24) contain channels that are similar to the pacemaker cells AND similar to the muscle myocyte cells, and therefore have electrical properties of both.

In the Fast Response, during the early repolarization step, K+ channels open.  What happens to them? We don't really seem to come back to them after they open. So far, they've been a pretty powerful channel. 

They play the same role in this action potential and membrane as they did in the neuronal system (that's why I didn't focus too much on them).  The are the repolarizers:  Their job is to repolarize the membrane allowing for the voltage-gated Na+ channels to recover from inactivation.  There are a variety of types of K+ channels in this system, but medically you do not need to know what they all are unless you go into cardiology, so I left out some of the intricate details.  They do, however, play the very important role of repolarizing the membrane.

Question 13: I may be reading this wrong, but I chose B as the answer because "Inward Na+ current" to me meant the flow of Na+ from outside to the inside. The correct answer on the power point is listed as D. 

I thought that depolarization means to get to a more positive state, so wouldn't na be going into the cell? I thought it would be answer B instead of D. 

The depolarization phase of the action potential from a ventricular muscle cell is produced by what?

            A.  Inward K+ current

            B.  Inward Na+ current

            C.  Inward Ca2+ current

            D.  Outward Na+ current

            E.  Outward Ca2+ current

Yes, this was one of the questions where the answer choices got mixed up, I apologize for that, but indeed the correct answer is B. Inward Na+ current causes the depolarization phase of the fast-response action potential that occurs in the ventricular muscle cells.  If the question was asking for the slow-response action potential that occurs in the SA or AV nodal cells, the correct answer would be C. Inward Ca2+ current.

5. Question # 14: The correct answer listed was E. Is it perhaps because K+ has just started efluxing meaning the membrane potential is just under the max voltage needed to cause another AP? 

can you explain to me why you can cause another ap at the plateau phase? bec/ i thought in cardiac muscles are don't cause another ap or we can't bec/ we need to let the heart pump everything out and then it will fill up again? 

I picked D, but the correct answer is supposed to be E. Could you please explain how come?

Also, the answer to #15 is not actually posted, what is the correct choice, I got E. (in retrospect, I think maybe the answer to 14 was not posted, and 15 is under #14 in the answer...)

 

 Which of the following is true regarding the plateau phase of the action potential from a ventricular muscle?

            A.  It is a result of Ca2+ flux out of the cell

            B.  It increases in duration as heart rate increases

            C.  It corresponds to the effective refractory period

            D.  It is the result of approximately equal inward and outward currents

            E.  It is the portion of the action potential when another action potential can most easily be elicited

Indeed, I apologize, the CORRECT answer for number 14 is D, NOT E.  As one student mentioned above this is EXACTLY the reason why tetany is not possible in cardiac muscles and therefore you have a contraction phase followed by a relaxation phase in the heart!

 

6) Also, the answer to #15 is not actually posted, what is the correct choice, I got E. (in retrospect, I think maybe the answer to 14 was not posted, and 15 is under #14 in the answer...)

15.  During which phase of the ventricular action potential is the membrane closest to the K+ equilibrium potential?

            A.  During the depolarization phase

            B.  During the ‘notch’ phase

            C.  During the plateau phase

            D.  During the repolarization phase

            E.  At rest

The correct answer for 15 is E. 

7) on number 8, 

  All of the following are correct regarding L-type calcium channels in cardiac ventricular muscle cells except which?

            A.  They are open during the plateau phase of the action potential.

            B.  They allow calcium entry that triggers sarcoplasmic reticulum calcium release.

            C.  They are found in the T-tubule membrane

            D.  They open in response to depolarization of the membrane

            E.  They contribute to the phase 4 of the pacemaker potential 

The answer is E but I thought that the L type and T type both do help at the end of phase 4 in the slow pacemaker response. I thought they helped the If channels. 

Phase 4 (pacemaker potential) - due to the closure of K⁺ channels and the opening of funny channels (depolarizing influx), T-type Ca²⁺ channels and L-type Ca²⁺ channels (Ca²⁺ influx).

That is right from the notes at the bottom so I am confused now. Any help would be appreciated.

Indeed, as I stated above in question #4, there is a bit of L-type Ca2+ contribution to the end of phase 4 of the pacemaker potential.  HOWEVER, ventricular muscle cells DO NOT HAVE a pacemaker potential.  This cell type only exhibits the fast-response action potentials and do not have the 'funny' channels or the T-type Ca2+ channels and do not exhibit this type of spontaneous depolarization.