>>Dr. Ketchum: The goal of this video is to study the sympathetic innervation to the SA
and AV nodes in the heart, and to see how this sympathetic innervation can regulate
heart rate. And so we begin just with an overview of the sympathetic innervation to the heart.
And when we think about sympathetic innervation, I’m going to take you back to previous chapters
when we talked about preganglionic neurons. And the neurotransmitter that is always
released from a preganglionic neuron is acetylcholine. The receptor on the postganglionic neuron—to
which acetylcholine will bind to—is a nicotinic cholinergic receptor. Now keep in mind that
the postganglionic neurons in the adrenal medulla have been modified and are now return—referred
to as chromatin cells. So when stimulated, the hormone that is released from these cells
is primarily epinephrine. Now keep in mind that the postganglionic neuron can also release
norepinephrine. Norepinephrine and epinephrine are both going to be binding to the beta-1
adrenergic receptor in the heart. And where are these beta-1 adrenergic receptors located
in the heart? They are located in the SA node, AV node, and the ventricular myocardium.
Please realize that the focus of this video is to look at sympathetic innervation to only
the SA and AV nodes, which again, our pacemaker cells are located there. So we’ll be altering
pacemaker potentials. Before we begin the mechanism for this process, let’s just recall
that a pacemaker potential, remember that it’s a pacemaker cells that are setting
the pace for the heart, which is dictated by the frequency of the pacemaker potentials
and pacemaker action potentials. And so keep in mind that—so if we alter the frequency
of these pacemakers, we alter the heart rate. So the sympathetic nervous system, we know,
is going to increase heart rate. So that means we have to have a higher frequency of pacemakers.
So let’s look at the mechanism for how this can happen. So just to remind you, this is
going to be the plasma membrane of the SA and the AV node, because we’re talking about
altering heart rate. Our neurotransmitter and/or hormone can be norepinephrine or epinephrine,
and the receptor is beta-1. Norepinephrine or epinephrine binds to your beta-1 receptor,
that’s going to activate a G protein. The G protein is going to slide over and it’s
going to activate adenylate cyclase. Remember, that’s the amplifier enzyme for the cyclic
AMP second messenger system. So that means ATP is going to be converted to cyclic AMP.
Cyclic AMP, then, is going to activate protein kinase. Protein kinase always phosphorylates;
so let’s look at what protein kinase is going to phosphorylate. Protein kinase, in
step six, is going to phosphorylate a funny channel and the T-type calcium channels. So
let’s look at the effect of this phosphorylation. So when protein kinase phosphorylates
the funny channel and the T-type calcium channels, that’s going to augment the opening. So
what this is going to do is that this is going to cause a faster slow depol. So in other
words, this cell will reach threshold faster. So the slope of it is going to be much steeper.
So on this graph, the sympathetic innervation is the blue line. The dotted line would be
normal. So look at the effect that augmenting the sodium and the voltage-gated T-type calcium
channels is having on slow depol. So slow depol here, notice how much faster that it is.
So when this happens, when these channels are augmented, what’s going to happen is
that’s going to end up—because they are responding faster, that means that’s going
to end up causing your voltage-gated potassium channels to close sooner, because these funnies
are opening sooner that they normally would. So that means voltage-gated potassium aren’t
going to stay open as long. If they close sooner, this tells us that repolarization
is going to be shorter than it normally would. So on the graph, okay, notice my shorter depol
or my shorter repol there. By having a steeper slope for depol, so in other words, slow depol
is faster by the repol being shorter, together then we’re increasing the frequency of these
action potentials. And when you increase the frequency of these action potentials, the
heart rate’s going to go up. And when the heart rate increases, cardiac output
will increase.