Cardio Phys: Lectures 1 &2 Flashcards
The resting membrane potential of cardiac cells is determined by what ion?
Potassium (K)
The conductance (g) at rest for K+ is high, and the conductance for Na+ is LOW at this level, so it contributes little to the resting membrane potential.
The membrane of a cell is becoming less negative. What is this process called?
Depolarization
What ion is mainly responsible for cell depolarization?
Na+
The influx of positive sodium ions causes depolarization to occur.
What is it called when the membrane becomes MORE negative?
Hyperpolarization
Cells become hyper polarized when the net movement of positive charges is extensive.
Cells of the atria, ventricles, and perkinje fibers have extended plateaus. What does this mean?
They have a “long” duration of action compared to the SA node.
Recall that for cells with longer durations of action, the refractory period (resetting of the membrane) is longer as well.
Which part of the heart has the shortest refractory period?
SA node has the shortest refractory period, and is therefore the PACEMAKER
Which part of the cardiac electrical conduction system has the fastest conductivity? Slowest?
Bundle of HIS has the fastest conductivity.
AV node has the slowest.
But having the fastest conductivity has nothing to do with refractory period, and the bindle of HIS has the LONGEST refractory period, and the AV node isn’t too far ahead of that.
Why don’t the fast Na+ channels in the SA node activate?
The lowest membrane potential SA nodal cells reach is -65 nV, and it doesn’t even stay that low for long due to the funny current (Gradual Na+ influx).
The inactivation gate of fast sodium channels is only open at membrane potentials below -60mV.
What ion is responsible for SA nodal cell depolarization?
Ca2+ channels (T and L-type)
What is a latent pacemaker?
AV node
Bundle of HIS
Perkinje fibers
All have the potential for automaticity (spontaneous depolarization), but the rule is that the pacemaker with the fastest rate of Phase 4 Depolarization controls the heart rate. SA node wins.
However, if the SA node is lost, one of the others will take over.
If the heart is being controlled by a latent pacemaker, what will happen to the heart rate? What is a latent pacemaker that is controlling the heart rate called?
It will be lower, because of the longer refractory periods of latent pacemakers.
Latent pacemakers that are actively controlling the heart rate are called ECTOPIC PACEMAKERS
Describe the effects of increased Parasympathetic stimulation (or decreased sympathetic stimulation) of the heart.
Decreased HR
Decreased conduction velocity (esp. in the AV node)
Decreased excitability of ectopic pacemakers
Describe the effects of increased sympathetic stimulation of the heart.
Increased HR
Increased Conduction Velocity (AV node mostly)
Increases excitability of ectopic pacemakers.
How does sympathetic stimulation increase the excitability of ectopic pacemakers?
Decreases (makes more negative) the threshold of Ca2+ channels
Example: Usually it takes the funny current a bit to reach -40mV, where T-type calcium channels can open and depolarize the SA node cells. A lower threshold = faster rate of consecutive depolarizations.
What effect with Acetylcholine stimulation have on the AV node’s Action Potential conduction rate? Norepinephrine?
Ach is a parasympathetic neurotransmitter.
Parasympathetic stimulation causes the heart rate to decrease, so the conduction rate of the AV node would decrease (take longer).
If Norepinephrine were increased, the signal transduction rate of the AV node would increase (be faster).
WHat is a typical heart rate?
60-70 bpm
What’s the point of AV delay?
AV delay is the slow conduction time of the AV node. (takes up almost half the time of a full contraction cycle) It allows the ventricles time to fill with blood before contraction.
What is the absolute refractory period? Explain the physiology behind it.
The absolute refractory period is during the plateau phase of an action potential, when the Na+ inactivation gates are all closed.
If the inactivation gates are closed, there can be no Na+ influx, therefore no depolarization, no matter how large a stimulus is administered.
The inactivation gates have to be below -60mV to open again, and regenerate an action potential.
Can extracellular calcium influx into a cell excite a contraction by itself?
NOPE –> but it can activate the SR to release enough calcium to cause contraction.
Inotropy means….
Degree of cardiac contractility
Chronotropy means
Heart rate
What NT has a positive inotropic and chronotropic effect?
Norepinephrine
Does Acetylcholine have a direct effect on inotropy? Chronotropy?
(Discussed in class)
Inotropy = contractility, and Ach doesn NOT have a direct effect. It has an indirect effect tho, because increased parasymp activity negates the sympathetic tone. There is decreased contractility due to removal of sympathetic stimulation, but NOT directly because of Ach.
Chronotropy = heart rate, and Ach has a direct effect. SLOWS IT
Why does a larger preload result in a more forceful contraction of the myocardial cells?
Larger preload (end diastolic volume) stretches the ventricular myocytes. The sarcomeres inside them get stretched as well, and when stretched, they are more sensitive to calcium. (more excitable)
What effect does End Diastolic volume have on end systolic volume?
None, up to a certain physiological point.
With a larger EDV, there is greater SV (stroke volume) due to increased force of contraction. (remember… stretched myocytes contract hard).
THE END SYSTOLIC VOLUME IS THE SAME
(see slide 23 of 2nd lecture for clarification)
If the sarcomeres of ventricular myocytes were shortened, what effect would this have on the stroke volume?
It would decrease. Short sarcomeres = less sensitive to calcium = weaker contraction.
Norepinephrine has greater affinity for what type of sympathetic receptor? What about Epinephrine?
Norepinephrine has greater affinity for alpha receptors.
(Vasoconstriction)
Epinephrine has affinity for both alpha and beta equally.
(Vasoconstriction and vasodilation)
Low levels of circulating Epinephrine cause ______________, while high levels cause ________________.
Why?
Low epinephrine levels = vasodilation
High epinephrine levels = vasoconstriction
Epinephrine has greater affinity for B2 at low concentrations, causing initial vasodilation. As levels increase, it also binds to alpha receptors, and the response generated by epinephrine at alpha receptors is greater than that of the B2 vasodilatory response. High levels cause vasoconstriction.
What effect will a high ventricular end diastolic pressure have on your risk of ischemic heart disease, especially of the left ventricle?
the coronary arteries get blood during DIASTOLE due to the mechanical compression of systole. If the ventricular end diastolic pressure is increased, there will be consistent resistance (due to compression) in the coronaries, and they won’t get oxygen, even during diastole.
This leads to increased risk of ischemia, and infarct for the left side of the heart.
What type of calcium channel is responsible for the depolarization/contraction coupling?
L-type (long lasting)
L-type calcium channels are activated after depolarization has caused the membrane potential to be POSITIVE.
What does a T-type Ca2+ channel do?
T-type calcium channels are open at LOWER membrane potentials, and are responsible for causing depolarization of the SA nodal cells once the funny Na+ current has made it reach the threshold.
Catecholamines have an inotropic effect. Explain this mechanism.
Inotropic effect = increased cardiac contractility.
Norepinephrine binds to B1 receptors, which are G-protein coupled receptors (Gs). Gs activates ADENYLYL CYCLASE, which increases the production of intracellular cAMP, which activates PKA, which phosphorylates things!
The things PKA phosphorylates:
- Ca2+ Uptake protein on the SR (takes in more intracellular calcium)
- Ca2+ channel on the cell membrane (more permeable to extracellular calcium
The ultimate goal is to increase intracellular calcium stores, which causes harder contraction.
By what mechanism does Acetylcholine slow heart rate? Does it effect contractility? (isotropy)
Ach binds to muscarinic receptors on the myocardial cells, which negatively effect adenylyl cyclase. No more cAMP production.
It causes activation of K(Ach) channels, which causes the membrane potential to hyperpolarize. It takes longer for the funny current (If) to make the cell reach the threshold for Ca2+ T-Type channels to open.
It also ??? (powerpoint?)
Dr. Hassid mentioned DIGOXIN in his lecture as a positive inotropic agent. What is this Cardiac Glycoside Drug’s MOA?
Positive inotropic = increase contractility.
Inhibits the Na+/K+ ATPase at the extracellular K+ binding site.
This disrupts the Na+ concentration gradient, and less Ca2+ is pumped out of the cell via the Na+/Ca2+ exchanger, resulting in increased intracellular stores of Ca2+.
The SR takes more Ca2+ up, and contractility is increased.
THIS INCREASES THE EJECTION FRACTION (Stroke volume is increased without the EDV increasing) MORE BLOOD TO THE PERIPHERY
When do you use Cardiac Glycosides like Digoxin?
Congestive Heart Failure –> a disease characterized by decreased contractility of ventricular muscle. (negative isotropy) The left ventricle is unable to eject a normal stroke volume.
Treatment: Positive Inotropic Drugs!
How do you physically monitor contractility?
Observe the Ejection Fraction (the fraction of the preload ejected during systole) –> usually 55%
If this number lowers, contractility is decreasing.
Remember: INCREASED CONTRACTILITY = INCREASED EJECTION FRACTION and Vice Versa
