Cardiac Muscles

Hello All,

There were not a lot of question, but a few.  Since that was my last lecture for you this semester, I also wanted to wish you all luck in your studies for the remainder of the semester!

Here's some confusing points on cardiac muscle:

1. I just wanted to clarify one thing, you said that the heart solely relies on oxidative phosphorylation for energy.  This is under normal conditions, but I think we learned from Dr. Smolanhoff  that under starvation circumstances it can get it's energy from glycolysis too?

As I indicated in class that there are back-up energy sources (there certainly need to be), but that under normal physiological conditions the heart needs to have a significant amount of oxidative phosphorylation and a constant source of ATP.

2. I want to make sure I understand the last slide of "Cardiac Muscle" lecture: Force vs Velocity Relationship.  

Here is my take:

"I think what this graph is trying to say is that the stronger the pushing out of the blood, the lower the afterload.  So the top of the chart (directly on the Y-axis) means there was a huge pumping burst and it leaves just a little bit of blood left into the heart (afterload).

Correct or way off?

Afterload is the pressure within the cardiovascular system that the heart needs to pump blood against.  It is the equivalent of the force that the muscle fibers need to produce in order to move an object.  Just as in skeletal muscles, an increase in force needed, a decrease in shortening velocity.  However, the interesting point is that an increase in preload allows the heart to pump against a greater afterload.  An increase in preload causes stretching of the muscle fibers, thereby increasing the maximum isometric tension, thereby allowing for the cardiac muscle fibers to produce more tension.

3.a.I have a out of the box question about the permeability graphs for the fast and slow response mechanisms. First question in regard to the slow response. Both the T and L type channels open but at different intervals in time. Is this mostly due to the thresholds that are required to open them? Also what is the significance of the spike in Ca+ permeability with the T-type? Does it have to do with decreasing permeability of K+ that is occurring at the same time?

In general, voltage-gated ion channels are opened by a change in voltage.  The voltage that causes them to open, however, varies.  The voltage that opens the If channels is hyperpolarized.  That allows for Na+ to flow into the cell, thereby depolarizing the membrane to a voltage that causes the T-type Ca2+ channels to open.  Influx of Ca2+ through the T-type Ca2+ channel then causes more depolarization of the membrane to a voltage that causes the L-type Ca2+ channels to open leading to the greater depolarization of the membrane.  There really is no significance in the spike in Ca2+ permeability through the T-type Ca2+ channels other than the fact that it causes the depolarization that opens the L-type Ca2+ channels.

3.b. Second question is the change in permeability of K+ in the fast response. It changes when the Ca+ channel is opened during the plateau phase. (it dips down then raises again) Is the change in permeability more due to the affect on the channels or the change in membrane potential because of the change in Ca permeability.

As I indicated in class, there are a variety of K+ channels in the cardiac muscles.  The K+ permeability indicates the total permeability for K+ in these cells through all of these channels.  Therefore, the permeability changes when different channels open and close not due to the changes in Ca2+ permeability.  The changes in Ca2+ permeability change the membrane potential and that can cause different K+ channels to open or close.

4. I'm really struggling with the question below because I know that an influx of Na+ causes depolarization:  Also, are Purkinje fibers and bundle of his considered slow or fast response? Where do they come in to play in all of this?

12.  Which of the following is the result of an inward Na+ current?
            A.  Upstroke of the action potential in the sinoatrial (SA) node
            B.  Upstroke of the action potential in Purkinje fibers
            C.  Plateau of the action potential in ventricular muscle
            D.  Repolarization of the action potential in ventricular muscle
            E.  Repolarization of the action potential in the SA node

Please refer to slide 23 for further information.  The Purkinje fibers are cells of the conducting pathway of the heart and have If conductances, T-type and L-type Ca2+ channels, voltage-gated Na+ channels and K+ channels.  Therefore, they have an action potential that is both slow and fast response.  They have the ability to have phase 4 depolarization and initiate their own action potential, but also have a fast depolarization due to the opening of voltage-gated Na+ channels and a delayed repolarization phase.

Therefore, with respect to that question, SA nodal cells do not have voltage-gated Na+ channels and, therefore, the influx of Na+ will not cause the upstroke of their action potential. Purkinje fibers, however,  do have a quick depolarization caused by the inward current of Na+.