Under normal conditions, which compartment (intracellular or extracellular) has the higher [K+]?
Intracellular-This is accomplished largely by the action of the Na/K ATPase pump.
For a resting, excitable but not automatic cell, which direction is the K+ leakage current, into or out of the cell?
Outward down a concentration gradient
If a patient has hypokalemia (low [K+] in blood and interstitial fluid), what will this do to the K+ leakage current?
By increasing the outward current concentration gradient it will lead to enhanced K+ loss from the cell leading to hyperpolarization (more negative “resting” membrane potential)
What would you predict to happen to cardiac cell membrane resting potential (Vm) in a patient with hypokalemia?
It would become more negative.
If a patient has significant hypocalcemia, what would you predict for calcium entry during the plateau phase of the action potential?
Reduced by virtue of a reduced concentration gradient.
What would you predict for the effect of hypocalcemia on the strength of myocardial contraction?
All other things being the same (other than calcium) this should reduce the strength of myocardial contraction by reducing the available free cytosolic calcium concentration, thus binding to troponin.
If a patient has significant hypocalcemia, what would you predict for calcium entry during the plateau phase of the action potential?
Reduced by virtue of a reduced concentration gradient.
What would you predict for the effect of hypocalcemia on the strength of myocardial contraction?
All other things being the same (other than calcium) this should reduce the strength of myocardial contraction by reducing the available free cytosolic calcium concentration, thus binding to troponin.
What phases (parts) of an action potential have the dominant effect on total action potential duration?
Phase 2 (plateau) and phase 3 (repolarization).
There is a genetic disorder in humans (Long QT Syndrome subtype 2) characterized by defective potassium channels (reduced K+ current). What phase of the action potential would be most affected and how would this affect action potential duration?
It would dominantly affect phase 3 repolarization, and it would retard that process. Would likely take longer for repolarization to be complete, prolonging the action potential. The “QT” part of the syndrome name refers to the simplistic way we assess this – as the time from the beginning of the QRS complex to the end of the T wave.
What would you predict for the effect of LQTS-2 on the refractory period duration for a myocyte?
It would tend to prolong the refractory period(s), both absolute and likely relative forms.
If you wanted to reduce the maximal heart rate of a patient, how might you manipulate normal potassium channels to achieve this effect?
As noted above, partial inhibition of K+ channels tends to slow repolarization, prolonging the action potential which likely includes the refractory periods. That would but a lower limit on the maximum number of action potentials that could occur per unit of time – lower maximal heart rate – at least in theory.
Which cells in the ventricles normally possess automaticity?
The SA node and Purkinje cells
Which cells depolarize faster, Purkinje cells or SA node?
The SA nodal automaticity range depolarizes much faster than Purkinje cells
What is the funny current?
a specialized, slow inward sodium/potassium current in the heart’s pacemaker cells (SA node) that triggers automatic, rhythmic electrical depolarization, setting the heart rate
Ivabridine is a drug that diminishes (but doesn’t abolish) the inward “funny” current of Na++ during phase 4 of SA nodal cells. What would you predict for it’s effects on heart rate?
This would reduce the slope of the spontaneous phase 4 depolarizations, hence reduce heart rate.
Sympathetic nerve stimulation augments the funny current and also promotes an inward Ca++ current during phase 4. What would the combined effects do to heart rate for the automatic cells of the SA node.
Augmenting the inward cationic currents speeds the spontaneous depolarization (increases the slope of Vm change). This would increase the rate of action potential genesis, or heart rate.
If you artificially pace the right atrium at high rates, it can have the effect to alter the action potential threshold to a less negative (closer to zero) value. Considering only this effect, how does this threshold effect alter the time it takes for the heart to resume it’s natural rate when pacing is abruptly stopped.
It would tend to slow heart rate.
How do the two major “bundles” of specialized conduction fibers function? Where does each one go?
They function to spread the action potential throughout both ventricles very quickly so the right and left
ventricles contract almost simultaneously.
One goes to the left ventricle (left
bundle), one to the right ventricle
An artificial pacemaker is basically a battery connected to a wire that touches the myocardium and delivers repetitive pulses of current that depolarize the cells touched by the wire. How does this work to get the entire heart to beat? What is the cellular
explanation?
This works by gap junction transmission of an action potential from one excitable cell to an adjacent cell.
If the left bundle is damaged to the point of total conduction failure, will the left ventricle get depolarized at all?
Yes. The normal right bundle will quickly depolarize the RV myocardium, and those cells (via gap junctions) will more slowly lead to LV myocardial depolarization. It’s less efficient in time and there is a small impairment in overall ventricular function because of it. As an isolated effect it’s probably not clinically significant in normal subjects. It can be important if the subject has myocardial weakness for other reasons.
If the left bundle is damaged as described above, what would you predict will happen to the QRS on the ECG. Specifically, what
would happen to the time duration for the entire QRS complex?
It will take longer for the QRS to be complete because it takes longer for all the myocardium to be depolarized. QRS duration is expected to increase
If the AV node is completely destroyed allowing no action potentials to reach the ventricles, the palpable arterial pulse rate will be very low.
First, how is even possible for the patient to survive if no atrial action potentials reach the ventricles?
Secondly, if we want to increase heart rate by using a pacemaker, where should we attach the “wire” (which chamber?)
Two sites in the heart have reliable automatic pacemaker function. The SA nodal cells, and Purkinje cells that behave as if they are near the ends of the ventricular Purkinje fibers (specialized conduction tracts). If the AV node fails completely, the SA nodal automaticity may be fine, but none of those action potential signals get to the ventricles. Fortunately the Purkinje cell automaticity takes over, but at a much slower heart rate – enough to keep the patient alive. If we want to use a pacemaker we need to attach the pacemaker wire (called a “lead”) to ventricular tissue. If attached to atrial tissue, those action potentials generated would suffer the same fate as any SA nodal action potentials. They would be blocked at the AV node and provide no effect to increase ventricular heart rate.
A normal relaxed myocyte has a very low
[Ca++]
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Cardiac Electrical Activity104
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Anatomy32
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Electric Coupling Discussion44
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Cardiac Radiography11
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Histology105
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Heart as a Pump76
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ECG33
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Endothelial Cell Function & Hemostasis62
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Normal Echocardiography17
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Particularities in Large Animals39
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Microcirculation28
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Control of Local Tissue Perfusion46
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Systematic Blood Pressure Control62
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Integration Across Systems6
