Cardiac Muscles

Hello All,

I have placed two files on the G-drive (or they will be transferred within a day or two) that are the animations for the slow-response and fast-response action potentials for the heart.  They are HTML files, so please open them within a web browser and they should play.

Here are some questions regarding Cardiac Muscles that I have gotten from you.  Same as previously, I have grouped 'like' questions together and provided a single answer.  Questions are in blue, answers in red.  As always, if there are additional questions you have please feel free to comment on this posting or to send them to me individually!

1.  When you have fast-response AP, the last step, phase 4, resting membrane potential is achieved when you have the inward rectifier channels stay open and allow potassium to leave? I looked up what recitifier channels do and it states how they allow positive charges to move inward or into the cells. This make sense grafically, but in the elcture it says potasssium will efflux. I am a bit confused about what exactly is going on the phase 4.

I have a question regarding the fast-response ventricular/atrial muscle AP. During phase 4, if the the inward rectifier K+ channels are open, doesn't that mean that the K+ are coming in?  Please, correct me if I am wrong, because on the slide it says Efflux. But it makes more sense to me that it should be an influx since the current is inward and that it is maintaining the membrane potential. If K+ is moving out, shouldn't it make the cell more negative and thus hyperpolarize rather than depolarize?

As I mentioned in class, the names of these channels seem quite confusing and you would think an inward rectifier channel would be moving ions into the cell.  In the case of the K+ channels, however, K+ is STILL moving down its electrochemical gradient OUT OF the cell thereby repolarizing the membrane potential.  Therefore, the efflux that is stated in the notes and on the slides IS correct.  These channels are named after activities that they perform in experimental situations and are therefore confusing medically.  As I also mentioned in class, your current understanding of the K+ channels being responsible for repolarization and maintaining the resting membrane potential is STILL correct! 

2.  From the lecture slide, it stated that the Na/Ca exchanger takes in Ca and put out Na.  But I thought it is the other way around?

I am unsure where you have seen that.  On slide 24 it has the arrow for Ca2+ moving out of the cell (against its concentration gradient) and Na+ to be moving into the cell (with its concentration gradient), thereby working as a secondary active transporter.

3.  Does the AP from the slow response and the fast response start at the same time?  

They both start at when the membrane hits threshold, if that is what you are asking, but is that at the exact same moment in time?  No.  Remember that in every system, the neurons, skeletal muscles, and the heart muscle cells, that the action potential is the electrical current that travels.  In the heart, that electrical current is initiated at the pacemaking cells (typically the SA nodal cells) and propagates/travels from there to neighboring cells through gap junctions.  Therefore, the depolarization is spread to the next cell which causes it to reach threshold and the action potential to fire.


4.  For excitation-contraction coupling, is it only the cardiac muscle in the myocardium contracting?

Yes.  As Dr. Yin and Dr. Moore have both mentioned, the conducting cells do not have very much of the contractile proteins contained within their cell membrane.  You need actin and myosin in order for contraction to occur, and it is the myocardium that contains the cardiac muscle cells that contain those contractile proteins that, therefore, allow for contraction to occur.

5.  Is it correct to say that for the same afterload, with increasing preload will result in larger/higher shortening velocity (Vmax)?

Yes, that is certainly another way of interpreting that relationship!

6.  So for the heart, is increasing EDV the same as saying increased in preload?  If this is the case then, increasing EDV (increasing preload) will allow the ventricle to overcome the afterload a lot quicker?

Increasing the EDV is indeed the same as increasing the preload.  Increasing the EDV would, therefore, allow the ventricle to contract against a given afterload quicker (similar to what you stated above).  However, it does not allow the ventricle to overcome a greater afterload any quicker, but simply allows the ventricle to produce enough tension to contract against a greater afterload. 

7. How are Slow L type Ca Channels able to open to produce the plateau phase in the fast response Action Potential (since wouldn’t Ca2+’s Nernst potential approximately equal the membrane potential at that stage in the action potential)?

L-type Ca2+ channels are a voltage-gated Ca2+ channel that are initiated to open around the threshold value (same as the voltage-gated Na+ channels and voltage-gated K+ channels that we studied in the neuronal action potentials).  They are slower to open, however, and take awhile to open.  By the time they open the Na+ channels have already opened and inactivated and one type of K+ channel has already opened causing the 'notch phase' of the cardiac muscle action potential.  The equilibrium potential for Ca2+, however, is typically VERY positive (around +100 mV) and at that point in the AP the membrane potential, due to the movement of Na+ into the cell and then some K+ out of the cell, is positive, but not as positive as the equilibrium potential for Ca2+.  Therefore, the electrochemical driving force for Ca2+ at that point is still for Ca2+ to come into the cell.  So, when the L-type Ca2+ channels open, Ca2+ influxes, counteracting the efflux of K+ and that causes the plateau phase.

8. I would like to clarify: are dihydropyridine receptors a type of L-type Ca channel or are they completely interchangable terms? Or am I completely mistaken and they are not related? 

I just had a quick question regarding the dihydropyridine receptor. Is this receptor the actual L-type Calcium or T-type Calcium channel or one of the two or is it a separate entity all by itself?  

L-type Ca2+ channel and dihydropyridine receptors are completely interchangable terms.  There are two different types of Ca2+ channels in the heart that we have discussed, the L-type Ca2+ channel and the T-type Ca2+ channel.  The DHP receptor is another name for the L-type Ca2+ channel and is the SAME CHANNEL as the L-type Ca2+ channel.  Therefore, it would be accurate to alternatively say that there is the T-type Ca2+ channel (present in those cardiac cells that have automaticity), and there is the L-type Ca2+ channel otherwise known as the DHP Receptor that is present in all cardiac cells of the heart.