PHYS-A5 ECG-1
The stimulus for the action potential can come from a variety of things, usually a neighboring cardiomyocyte, but it can also be any of the conduction pathway fibers discussed above. The wave of depolarization will enter a given cardiac muscle cell via the gap junction. Phase 0-1
Rapid depolarization is caused by sodium entry into the cell, just like in skeletal muscle. Very fast acting sodium channels quickly open up, flood the cell with sodium and then quickly close; so there is a spike in the membrane potential seen on the top graph (red line). With the channels closed, permeability to sodium now drops.
Relative pacemaker rates SA node AV node Purkinje fibers
SA node (70-100 bpm), AV node (40-60 bpm), Purkinje fibers (15-40 bpm)
The SA node
Sets the pace of the heartbeat, i.e. "pacemaker of the heart".
SCOUT PIN
Sodium & Calcium higher OUTside, Potassium higher INside
T-type -- channels allow calcium ions to -- into the cell.
T-type CALCIUM channels allow calcium ions to MOVE into the cell.
Fast response occurs in cardiomyocytes AKA myocardial contractile cells.
The His-Purkinje network looks a little bit like this, but this is mostly your myocardial cells. Rapid spike similar to skeletal muscle, followed by a plateau phase (unique to cardiac m.), repolarization phase, return to baseline
The following is unique to the cardiac muscle cells. There are slower, voltage-gated calcium channels (L-type) that open up in response to this depolarization. Phase 2
The opened calcium channels allow calcium to enter the cell, which causes a plateau phase, where the cell membrane remains depolarized. The potassium channels are also inhibited, so there's not much potassium leaving the cell, which helps to maintain the plateau. You don't see this plateau in skeletal muscle, or in the autorhythmic cardiac cells. Eventually the voltage gated calcium channels begin to close.
The atrioventricular node (AV node) slows conduction to 1/20 of the conduction speed of normal myocardium. This is called the nodal delay.
This gives the atria time to depolarize, contract, and force more blood into the ventricles for that extra bit of filling.
If the SA node isn't working properly, then the AV node is ready to take over.
This is one reason why people get artificial pacemakers - their SA nodes may not be functioning properly.
AV nodal delay is important physiologically.
When the atria depolarize this leads to contraction of the muscle. The contraction puts pressure on the blood in the atria and causes blood to move down from the atria to the ventricles. This happens before the ventricles contract and allows for additional filling of the ventricles. This "extra kick" of atrial blood into the ventricles is especially useful during exercise because it dramatically affects cardiac output. So it's very important that the atria contract before the ventricles do.
T-type Ca+ channels, think (T)hreshold
allow calcium ions to move into the cell.
Action potential:
an "all-or-none" sequence of changes in membrane potential resulting from an all-or-none sequence of changes in ion permeability due to the operation of voltage-gated Na+ and K+ channels. *Remember, sodium and calcium are higher outside the cell, and potassium is higher inside the cell.
Look at the relative velocities of conduction and note that the
conduction through the SA and AV nodes is actually slower than cell-to-cell conduction in the myocardium. The Bundle of His conducts twice as fast as myocardium, and the Purkinje system is 4X aster!
Autorythmic "pacemaker" cells initiate the
heart beat
SA node sets the pace of the
heartbeat 70-100
Slow response cells (SA and AV nodal cells)
o No resting membrane potential o Gradually approach threshold without any neural input o Depolarization is less rapid than fast response o Repolarization with no plateau
Fast response cells= contractile cells
o Rapid depolarization o Plateau phase o Repolarization phase
In contractile cells:
o Rapid depolarization is caused by entrance of sodium into the cell. o Then, calcium slowly enters the cell, resulting in the plateau phase of the action potential. o Finally, potassium ions exit the cell, causing repolarization and movement towards resting membrane potential.
Electrical signals travel through the conduction pathway
o SA node o Atrial internodal pathways o AV node o AV Bundle (Bundle of His) o Left and right bundle branches o Purkinje Fibers
Steps of Electrical conduction
o SA node depolarizes o Electrical activity goes rapidly to the AV node by intermodal pathways o Depolarization spreads more slowly across the atria. Conduction slows through AV node (AV nodal delay= 1/20 conduction speed of normal myocardium) This allows for complete filling of the ventricle. o Depolarization moves rapidly through ventricular conducting system to the apex of the heart o Depolarization wave spreads upward from the apex (so ventricles contract from bottom to top)
When the cell membrane potential reaches threshold, voltage-gated L-type calcium channels
rapidly open and allow more calcium to enter quickly, causing the rapid depolarization phase.
Potassium efflux plus the closing of calcium channels are responsible for the --
repolarization phase.
This results in summation of the contractions, and eventually
tetanus (when the tension is maxed out).
In cardiac muscle, the plateau phase caused by calcium prevents the cell from repolarizing quickly. The cell therefore has a longer refractory period.
the refractory period is almost as long as the cardiac muscle contraction-relaxation cycle.
The refractory period occurs when the cell is unresponsive to further stimulation.
the refractory period is the time needed for the cell to repolarize so that it can respond to another depolarization.
In skeletal muscle, the refractory period is short because the upstroke caused
upstroke caused by sodium influx is quickly reversed by potassium efflux. The membrane potential returns to its resting point of -90mV within 10 msec. Meanwhile the muscle is still contracting.
Purkinje fibers "zap" the surrounding cells with the AP so that all of them can work; this is important because
we want the heart to be able to push blood up and out. Even if there were no Purkinje fiber network the AP will still be able to get to the apex. Depolarization will still come from the bottom up but be very slow and there would be no strong force contraction to push the blood out of the ventricles.
Fast Response Phases
0: Sodium channels open (depolarization) 1. Sodium channels close 2. Calcium channels open; fast Potassium channels close 3. Calcium channels close; slow Potassium channels open (repolarization) 4. Resting period
Action potential of an autorhythmic cardiac cell
1) Driven by a pacemaker potential, and autorhythmic cells do not have a steady resting membrane potential. The pacemaker potential goes down to a minimum membrane potential and gradually approaches threshold because of leaky ion channels.
1) Which is a mechanism by which the parasympathetic nervous system increases pacemaker activity (decreases HR)? a. The threshold potential becomes more positive b. The threshold potential becomes more negative c. The pacemaker potential becomes more positive d. The pacemaker potential becomes more negative e. A & C
1) D—Parasympathetics hyperpolarize pacemaker cells, which means that the pacemaker potential (remember, pacemaker cells don't have a resting membrane potential) is more negative.
Extrinsic innervation of the heart
1) NOT necessary for contraction. 2) The heart is extrinsically innervated by the ANS: 1. Parasympathetic cardioinhibitory center inhibits heart- i.e. decreases heart rate, reduces blood exiting heart, etc.) 2. Sympathetic cardioacceleratory center stimulates the heart a. Both are located in the medulla. 3. Heart rate is modulated by (1) impacting the autorhythmic firing rate of SA node and (2) slowing or increasing transmission of the action potential through the AV node. More about this will be discussed in future lectures.
What initiates action potentials in cardiac muscle?
1) Specialized "pacemaker" cells (SA/AV nodes) 2) Generate spontaneous action potentials 3) Depolarization rapidly spreads to adjacent contractile cells via gap junctions
Why is the AV node not the pacemaker?
1. Although the AV node and Purkinje fibers are also autorhythmic, they never really have time to reach their own autorhythmic potential. The AV node just receives the (faster) signal from the SA node, which triggers the AV node to depolarize and pass on the signal. This is why the SA node is the pacemaker of the heart.
1) Which of the following is the result of an inward Na+ current? (BRS Physiology, 6th Edition) 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
1. B. The upstroke of the action potential in the atria, ventricles, and Purkinje fibers is the result of a fast inward Na+ current. The upstroke of the action potential in the SA node is the result of an inward Ca++ current. The plateau of the ventricular action potential is the result of a slow inward Ca++ current. Repolarization in all cardiac tissues is the result of an outward K+ current.
The AV node
1. Provides a path of electrical transmission to the ventricles 2. Delays the transmission of action potentials so that there's time for the ventricles to fill.
Purkinje fibers very quickly spread the depolarization wave upward from the apex.
1. Purkinje fibers conduct the signal 4-6x faster than the normal myocardium. Bundle branches are fast, but Purkinje fibers are super-fast. 2. As the action potential spreads from the apex upwards through the myocardium, the squeezing is able to travel from the apex towards the top of the ventricles. Remember, the pulmonary and aortic valves are located at the top of each ventricle, so squeezing from the apex towards the base maximizes the ejection of blood. Purkinje fibers (15-40 bpm)
The Purkinje fiber network
1. Rapidly transmits depolarization to the ventricles for organized contraction, from the apex upwards towards the base. 2. The travel time for the action potential to go from the start of the bundle branch to the end of the Purkinje network is 0.06 sec. This is represented by the QRS complex on an EKG. The reason the QRS is so tight in a healthy person is the rapidness of the Purkinje Fiber network.
Parasympathetic nerve fibers terminate in the SA and AV nodes but not really in the actual muscle parts of the heart. Parasympathetics slow down the heart rate by
1. Releasing ACh, which binds to muscarinic receptors (M2-receptors which are G-protein coupled receptors) on autorhythmic cells. 2. This results in an INCREASE in potassium efflux and a DECREASE in calcium influx 3. The cell becomes HYPERPOLARIZE and takes longer to reach threshold and thus depolarization, ultimately leading to 4. Slower heart rate.
Sympathetic nerve fibers have terminations in the SA and AV nodes, ALL OVER the ventricular myocardium, and only a little in the atrial myocardium.
1. Releasing norepinephrine, which binds to B1-receptors on autorhythmic cells (Remember B1-receptors are G-protein coupled receptors used in second messenger systems - from Dr. Molina's ANS lecture) 2. This results in an INCREASE in sodium and calcium influx 3. The rate of depolarization increases in the cell and drives the "threshold graded DEPOLARIZATION" to occur faster (QUICKER sodium and calcium influx) 4. Action potential occurs more quickly and gets spread out through the conduction pathway, causing faster heart rate
Skeletal muscle action potential.
1. The resting membrane potential is a little less negative than in the heart. 2. A depolarization is stimulated by a motor neuron (different from what happens in the heart) 3. The depolarization causes the sodium channels on the membrane to open up. Since sodium is greater outside the cells it pours down its concentration gradient into the cell, causing a rapid depolarization of the cell. (The cell is at a negative resting membrane potential, and positive ions are flowing in and counteracting that—causing depolarization.) Upstroke is due to sodium influx. 4. Sodium channels slam shut pretty quickly, and potassium channels open up. So you have increased permeability of the membrane to potassium towards the end of the AP. 5. Potassium is higher inside the cell, so potassium travels down its concentration gradient, OUT of the cell, causing a repolarization. Return to resting potential is due to potassium efflux.
The AV Bundle/Bundle of His connects the AV node to the bundle branches
1. This is the only pathway from the atria to the ventricles because the AV valves are fibrous insulators and don't transmit the action potential well. E. Depolarization moves rapidly through the left and right bundle branches to reach the apex of the heart, where the action potential flows into the Purkinje fiber network
Slow response occurs in
1. occurs in SA node and AV nodal cells. 2. Rather than having a resting membrane potential, slow response cells have a "decay towards threshold." This is what leads to the autorhythmicity of these cells. The cells gradually approach threshold without any neural input. When they reach threshold, they depolarize. 3. Note that the depolarization of the slow response cells is not a fast spike like in the fast response (myocardial) cells. This has to do with the ion channels present. The cell then repolarizes and approaches a baseline, but it never maintains a stable membrane potential.
2) In the sinoatrial (SA) node, phase 4 depolarization (pacemaker potential) is attributable to (BRS Physiology, 6th Edition) a. An increase in K+ conductance b. An increase in Na+ conductance c. A decrease in Cl- conductance d. A decrease in Ca++ conductance e. Simultaneous increases in K+ and Cl- conductance
2. B. Phase 4 depolarization is responsible for the pacemaker property of the SA nodal cells. It is caused by an increase in Na+ conductance and an inward Na+ current, which depolarizes the cell membrane.
3) The different phases of an action potential are due to the influx or efflux of different ions. Which of the following pairs is mismatched? a. Depolarization of fast-response/contractile cells—Na+ influx b. Plateau phase of contractile cells—Ca2+ influx c. Repolarization of fast-response cells—K+ efflux d. Slow, "leaky" depolarization towards threshold in autorhythmic cells—Ca2+ and Na+ influx e. Depolarization of slow-response/autorhythmic cells—Ca2+ influx f. Repolarization of slow-response/autorhythmic cells—K+ efflux g. All of the above are correctly matched h. Only E is correctly matched
3) G, all of the above are correct!
3) The low-resistance pathways between myocardial cells that allow for the spread of action potentials are the (BRS Physiology, 6th Edition) a. Gap junctions b. T tubules c. Sarcoplasmic reticulum d. Intercalated disks e. Mitochondria
3. A. The gap junctions occur at the intercalated disks between cells and are low-resistance sites of current spread.
4) Which of the following is false concerning the electrical conduction system of the heart? a. The SA node has a faster autorythmic rate than that of the AV node. b. The influx of Calcium into the cell is primarily responsible for the plateau phase in autorythmic cells. c. Cell-to-cell conduction in cardiomyocytes is slower than conduction through Purkinje fibers d. Electrical activity of the heart can be regulated by the sympathetic AND parasympathetic nervous system
4) B--- Calcium is responsible for the plateau phase in contractile cells. Autorythmic cells do not show a plateau phase.
4) Myocardial contractility is best correlated with the intracellular concentration of: (BRS Physiology, 5th Edition) a. Na+ b. K+ c. Ca++ d. Cl- e. Mg++
4. C. Contractility of myocardial cells depends on the intracellular concentration of Ca++, which is regulated by Ca++ entry across the cell membrane during the plateau of the action potential and by Ca++ uptake into and release from the sarcoplasmic reticulum. Ca++ binds to troponin C and removes the inhibition of actin-myosin interaction, allowing contraction (shortening) to occur.
5) The low-resistance pathways between myocardial cells that allow for the spread of action potentials are the a. Gap junctions b. T-tubules c. Sarcoplasmic reticulum (SR) d. Intercalated disks e. Mitochondria
5) A---The gap junctions occur at the intercalated disks between cells and are low-resistance sites of current spread [BRS Physiology-4th edition]
5) The physiologic function of the relatively slow conduction through the atrioventricular (AV) node is to allow sufficient time for: (BRS Physiology, 5th edition) a. Runoff of blood from the aorta to the arteries b. Venous return to the atria c. Filling of the ventricles d. Contraction of the ventricles e. Repolarization of the ventricles
5. C. The atrioventricular (AV) delay (which corresponds to the PR interval) allows time for filling of the ventricles from the atria. If the ventricles contracted before they were filled, stroke volume would decrease.
6) 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
6) B--- The upstroke of the action potential in the atria, ventricles, and Purkinje fibers is the result of a fast inward Na+ current. The upstroke of the action potential in the sinoatrial (SA) node is the result of an inward Ca2+ current. The plateau of the ventricular action potential is the result of a slow inward Ca2+ current. Repolarization in all cardiac tissues is the result of an outward K+ current. [BRS physiology-4th edition]
6) Which receptor mediates slowing of the heart? (BRS Physiology, 5th edition) a. α1 receptors b. β1 receptors c. β2 receptors d. Muscarinic receptors
6. D. Acetylcholine (ACh) causes slowing of the heart via muscarinic receptors in the sinoatrial (SA) node.
Atrial internodal pathways transfer the action potential very quickly to the atrioventricular node
At the same time, depolarization begins to spread slowly across the atria, causing it to squeeze.
In autorhythmic cardiac cells, -- is responsible for the upstroke in the action potential, not sodium like in contractile cardiac or skeletal muscle cells.
CALCIUM
The sinoatrial node (SA node) depolarizes, generating an action potential
Cells of the SA node are autorhythmic pacemaker cells. The SA node is the pacemaker of the heart in a healthy individual. Think "normal sinus rhythm." It sets the rate for the rest of the heart.
AV node provides path of electrical transmission to ventricles.
Delays transmission of action potentials to allow filling of ventricles. 40-60 BPM
F-type [funny] channels allow -- ions to -- into the cell while T-type calcium channels allow calcium ions to move into the cell.
F-type [funny] channels allow SODIUM ions to "LEAK" into the cell while T-type calcium channels allow calcium ions to move into the cell. These two channels together slowly depolarize the cell to its threshold—a "threshold graded depolarization"
Phase 3-4
Finally, the potassium channels open up, potassium rapidly exits the cell, and causes the repolarization. The cell membrane potential returns to baseline. Resting membrane potential varies depending on cell type.
The physiological significance of the long refractory period in cardiomyocytes, which is due to the calcium plateau, is that the heart muscle cannot be stimulated again before it has relaxed: The heart does not exhibit summation or a tetanus response.
If the heart was in a constant state of contraction it would not be able to pump blood so it needs a coordinated relaxation and contraction cycle.
This means that if the skeletal muscle receives another stimulus, it will depolarize again, triggering another contraction. In skeletal muscle, many stimuli can be received in quick succession.
In skeletal muscle, many stimuli can be received in quick succession.
The plateau is important in cardiac cells because it results in a longer refractory period.
In this period, the cells can't be stimulated by another action potential. This keeps the cells from contracting over and over in quick succession (a process called summation which can result in a maximal contraction called tetanus).
