Cardiac Electrophysiology

Front 1

1. What are the two types of muscle cells found in the heart?

Back 1

Contracting cells- These are the majority cells found in atrial and ventricular tissues.

Conductive cells-These cells make up the tissues of the SA node, the bundle of His and the Purkinje system.

Contracting cells generate most of the cardiac force.

Front 2

2. List the sequence of activated tissues in the cardiac action potential.

Back 2

SA node----Atrial internodal tracts and atria-----AV node------Bundle of His-------Purkinje system-----ventricles.

Front 3

3. The action potential spreads from the SA node to the right and left atria via the----------------------.

Back 3

Atrial internodal tracts. Simultaneously, the action potential is conducted to the AV node.

Front 4

4. What is the purpose of slow conduction through the AV node?

Back 4

Conduction is slow as to ensure that ventricles have enough time to fill with blood, before they are activated and contract.

Obviously, any increase in conduction velocity can result in decreased ventricular filling and a lessened stroke volume and cardiac output.

Front 5

5. Ventricular action potential diffuses from one cell to another via low resistance pathways located between the cells. True/False

Back 5

True.

Front 6

6. What physiological characteristics must be intact to qualify as normal sinus rhythm?

Back 6

1. The action potential must come from the SA node.

2. SA nodal impulses must activate in a regular and consistent manner, and at a rate of between 60-100 impulses per minute.

3. Myocardial activation must occur in the proper sequence and with the correct timing and delays.

Front 7

7. What actually determines the cardiac action potential?

Back 7

This is determined by the relative conductances or permeability to ions and the concentration gradients for the ions.

Front 8

8. What would typically occur if the cell membrane has a high conductance or permeability to an ion?

Back 8

The ion should flow down its electrochemical gradient and attempt to drive the membrane potential towards an equilibrium potential (Nernst equation).

Front 9

9. Membrane potential is expressed is normally expressed in millivolts. True/False

Back 9

True. The intracellular potential is expressed in comparison to or relative to extracellular potential.

A membrane potential of -85mV, means 85mV, cell interior negative.

Front 10

10. Cardiac resting membrane potential is chiefly determined by which ion?

Back 10

Potassium. The conductance to potassium at rest is high, and the resting membrane potential is close to the potassium equilibrium potential.

Na+ contributes little, since the membranes conductance to sodium is low.

Front 11

11. Regarding cardiac action potential stability, what is the function of Na+-K+ ATPase?

Back 11

It maintains Na+ and K+ concentration gradients across the cell membrane.

Front 12

12. Define depolarization.

Back 12

This means that the membrane potential becomes less negative. This occurs when there is a net movement of positive charge into the cell(inward current).

Front 13

13. Define hyperpolarization.

Back 13

This indicates that the membrane potential becomes more negative, and this occurs when there is net movement of positive charge out of the cell. (outward current).

Front 14

14. What occurs if there is a decrease in the extracellular potassium concentration on the resting membrane potential of a myocardial cell.

Back 14

In this case, the K+ equilibrium potential should become more negative. K+ ions will flow out of the cell and down the now larger electrochemical gradient driving the resting membrane potential (RMP) toward the new, more negative potassium equilibrium potential.

Front 15

15. The resting permeability of ventricular cells to Na+ is low, and sodium minimally contributes to the RMP. True/False

Back 15

True.

Front 16

16. What is occurring during the upstroke of the ventricular action potential?

Back 16

Na+ conductance increases, and sodium flows into the cell down its electrochemical gradient, and the membrane potential is briefly driven toward the sodium equilibrium potential (depolarized).

Front 17

17. What is Threshold potential?

Back 17

This is the potential difference where there is a net inward current(inward current becomes greater than the outward), Here, the depolarization becomes self sustained and gives rise to the upstroke of the action potential.

Front 18

18. What is Na+-K+ ATPase, and what is its function?

Back 18

This is present in the membrane of all cells.It pumps the Na+ from the ICF to ECF and K+ from ECF to ICF. For every three sodium ions pumped out of the cell, two K+ ions will be pumped into the cell. More positive charge is pumped out of the cell. This is called an electrogenic process. It creates a potential difference.

Proper concentration gradients are maintained for both Na+ and K+.

Front 19

19. The Na+-K+ ATPase has an alpha and beta subunit. Define these units.

Back 19

The alpha subunit has ATPase activity as well as binding sites for the transported ions, Na+ and K+.

The beta subunit may play a role between the E1 and E2 state.

Front 20

20. Differentiate between the E1 and E2 state.

Back 20

The Na+-K+ ATPase can change between two fundamental conformational states, E1 and E2.

In the E1 state, the binding sites for sodium and K+ face the intracellular fluid, and the enzyme has a high attraction for sodium.

In the E2 state, the binding sites for Na+ and K+ face the ECF, and the enzyme has a high attraction for K+. This whole process is powered by ATP hydrolysis.

Front 21

21. What is Oubain and digitalis?

Back 21

These are cardiac glycosides. These drugs inhibit Na+-K+-ATPase. The intracellular na+ concentration will increase, and the intracellular K+ concentration will decrease. these drugs inhibit the Na+-K+ ATPase by binding to the E2-P near the K+ binding site on the extracellular side, preventing the conversion of E2 baqck to E1.
They disrupt phosphorylation and dephosphorylation.

Front 22

22. Regarding action potentials of the ventricles, Atria and the Purkinje system, the action potentials in these tissues are of long duration. True/False

Back 22

True. AP duration varies from 150msec in the atria, to 250 in the ventricles, to 300 msec in the Purkinje fibers. The longer the AP, the longer is the refractory period to firing another AP.

Front 23

23. Though the Purkinje fibers are relatively stable, can they develop unstable resting membrane potentials in certain conditions?

Back 23

They can. They can become, though rare, the heart's pacemaker.

Front 24

24. The action potential in cardiac cells, is characterized by a plateau. What does this mean?

Back 24

The plateau is actually a sustained period of ongoing depolarization. This is responsible for the long duration of the AP, and the longer refractory periods.

Front 25

25. Describe phase 0, or the upstroke of the cardiac AP plateau of ionic Na+.

Back 25

The AP starts with a phase of rapid depolarization, referred to as the upstroke. This upstroke is caused by a increase in Na+ conduction (gNa+) This is produced by depolarization induced opening of activation gates on the Na+ channels.

There is an inward sodium current(INa+), which drives the membrane potential toward Na+ equilibrium potential of about 65mv.

Front 26

26. In reference to Na+ membrane potential, in phase 0, does the membrane actually reach Na+ potential?

Back 26

It does not. This is due to the inactivation gates of the Na+ channels, which close in response to depolarization. The sodium channels open briefly and then they quickly close.

At the peak of the upstroke, the membrane potential is depolarized to about 20mV.

Front 27

27. In Cardiac AP, what is the significance of dV/dT?

Back 27

This is the rate of the rise of the upstroke. dV/dT is the rate of change of the membrane potential, as a function of time, and its units are in volts per second. (V/sec) dV/dT will vary depending on the resting membrane potential.

Front 28

28. Describe phase 1 of cardiac AP.

Back 28

This is a short period of repolarization, which follows the upstroke. Here there must be a net outward current.

1. The inactivation gates of the sodium channels close in response to depolarization. When these gates close, gNa+ decreases and the inward sodium current, stops.

2. there is an outward potassium current. At upstroke peak, both electrical and chemical driving forces K+ movement out of the cell. There is more intracellular K+ The cell interior is electrically positive.

Front 29

29. Describe phase 2 of the cardiac AP.

Back 29

In phase 2 there is an increase in cacium conduction (gCa2+), which results in a inward calcium current. This is a slow inward current.

The Ca+ channels that open during the plateau are called L-type channels. These channels are inhibited by Ca+ channel blocker medications, such as Nifedipine, Diltiazem and Verapamil.

To balance this inward Ca+ current, there is an outward K+ current. The net current at this point in time is actually zero.

Ca+ is released from intracellular stores for excitation-contraction coupling.

Front 30

30. Describe phase 3, repolarization of the cardiac AP.

Back 30

Repolarization begins at the end of phase 2. Repolarization occurs when outward currents are greater than inward currents. During this phase, repolarization results from both a decrase in gCa+, and an increase in gK+, to even higher levels than at rest.

Front 31

31. Describe phase 4, resting membrane potential, electrical diastole.

Back 31

The membrane potential fully repolarizes during phase 3 and returns to the resting level of about -85mV. During this phase, the membrane potential is stable again, and the inward and outward currents are equal.

The resting membrane potential approaches, but does not fully reach, the K+ equilibrium, which reflects the high resting conductance to K+.

Front 32

32. Regarding the sum of inward Na+ and ca+ currents, how can these be of the same magnitude as the outward K+ current given that gNa+ and gCa+ are very low, and gK+ is very high.

Back 32

Actually, for each ion, current =conductance X driving force. Even though gK+ is high, the driving force on K+ is low because the resting membrane potential is close to the K+ equilibrium. The outward K+ current is small.

gCa+ and gNa+ are both low, and the driving forces of both Na+ and Ca+ are high, because the resting membrane potential is far from the sodium and Ca+ equilibrium potentials. The sodium and calxium current is equal to the K+ outward current.