>>Dr. Ketchum: In this video, you’re going to learn how the sympathetic innervation to
the ventricular myocardium can increase contractility in the heart. And so just to re—remind you
of sympathetic innervation to the heart, please test yourself and pause the video and then
fill in these steps. So I’m going to go ahead and just quickly review these for you
once again. When the neurotransmitter—what neurotransmitter is released from the preganglionic
neurons? We know that will always be acetylcholine, and we know that the receptor on the postganglionic
neuron to which acetylcholine will bind to is nicotinic cholinergic. Remember the postganglionic
neurons in the adrenal medulla have been modified, and those are referred to as chromaffin cells.
Now the chromaffin cells, when stimulated, release a hormone—primarily epinephrine.
Epinephrine then will bind to beta-1 adrenergic receptors in the heart, and these receptors
are located in the SA and AV nodes in the heart, as well as the ventricular myocardium.
Now please understand that when we talk about sympathetic innervation, we do have epinephrine
released from the chromaffin cells. There’s also norepinephrine being released from the
postganglionic fibers as well. What we would like to look at then is how the sympathetic
nervous system increases contractility in the heart. Let’s go ahead first and,
and be sure you understand where we are in the heart. This would be the plasma membrane
of the myocardium, the ventricular myocardium. Remember, the myocardium is the heart muscle.
We know that we have a beta-1 adrenergic receptor, and we know that norepinephrine or epinephrine
can bind to that beta-1 adrenergic receptor. So let's begin with this mechanism.
So epinephrine and norepinephrine bind to the beta-1 adrenergic receptor. That’s going
to activate your G protein, and that activated G protein then will activate your amplifier
enzyme called adenylate cyclase. And adenylate cyclase, we know, will catalyze the conversion
of ATP into cyclicAMP, which then activates protein kinase. And we know protein kinase
phosphorylates. So when we look at the effect of contractility, there are four ways in which
epinephrine or norepinephrine can increase contractility, and these are all done by protein
kinase. So let’s look at protein kinase, PK, and let’s see what is phosphorylated
by protein kinase and how that can increase contractility. Protein kinase can phosphorylate,
or does phosphorylate the L-type calcium channel on the sarcolemma. Remember, this is a voltage-gated
L-type calcium channel on the sarcolemma. So when this happens, then that augments the
channel, so that means now we have increased calcium influx into the cytosol. And we know
if we have increase calcium influx into the cytosol, there’s more that can bind to troponin,
and that will increase the force of contraction. Protein kinase can also phosphorylate the
calcium channel on the SR. So when that happens that channel is too augmented, which also
increases calcium influx into the cytosol, which increases the force of contraction.
So those are two of the four things that are going to increase the force of contraction,
and therefore alter contractility.
The third thing is that protein kinase will phosphorylate the myosin. So when it phosphorylates
the myosin, that’s going to increase the activity of myosin ATPase. So what that means,
then, is we can hydrolyze ATP faster, which means we can increase the rate of crossbridge
cycling. And if we can increase the rate of crossbridge cycling, that’s going to increase
contractility.
Okay, so those are three things. Let’s look at the fourth item that increases contractility,
and that is phosphorylation of the calcium ATPase. So calcium ATPase, remember, is on
the SR. And so by phosphorylating calcium ATPase, that means that it can reuptake calcium
at a faster rate. Here’s an important concept for you; cardiac muscle has to completely
relax before it can contract again. There is no summation. There is no incomplete tetanus
or complete tetanus in cardiac muscle. The heart must relax completely before it can
contract again. The reason for that is you want to give the heart time to fill with blood,
and the only time that the ventricles will fill with blood is when the heart or when
the ventricles are in a relaxed state. So if we increase the rate of reuptake that means
that the muscle can relax at a faster rate. And if it can relax quicker, then all of these
other events can occur again quicker.
So all together, all four of these then are going to increase contractility. So this concludes
the video on how the sympathetic nervous system increases contractility in the heart.