2.2.2 Abnormal Cardiac Electrophysiology

Question 1

What is the mechanism by which hypoxia will affect an action potential in the tissue?

Answer 1

Insufficient O2 will decrease ATP formation. L-type Ca++ must be phosphorylated during each action potential to allow Ca++ through. Decreased ATP will impair the Ca++ current which will decrease the duration of the action potential.

Question 2

Long QT syndrome can be cause by?

Answer 2

Decreased Na or K current

Question 3

Why is V (membrane potential) being pushed towards E_Na during hypokalemia?

Answer 3

The decreased gK is increasing the fgNa. Increasing the conductance to an ion moves the membrane potential to the Nernest potential of that ion.

Question 4

How does the conductance of potassium relate to the concentration of potassium outside the cell?

Answer 4

It is directly related. As potassium concentration increases outside the cell so does the conductance

Question 5

Why are M cells more susceptible to problems with action potentials?

Answer 5

Action potential prolongs disproportionately relative to the action potential of other ventricular myocardial cells in response to slowing of rate and or in response to action potential prolonging agents.

Less potassium current - less repolarizing current that prolongs phase 2

Larger Na-Ca exchange current - provides inward current to prolong phase 2

Question 6

What is the Nernst potential formula?

Answer 6

Question 7

What is the mechanism by which calcium corrects hyperkalemia?

Answer 7

Increased calcium produces a positive shift in the Na channel inactivation curve. Calcium also produces a positive shift in the Na channel inactivation curve. This shift can be utilized to recover some excitability by converting inactive sodium channels back to the resting state and increasing the current of sodium.

Question 8

How will insulin act as a regulator of potassium?

Answer 8

Direct stimulation of the Na-K pump by insulin will also act to move potassium into the cell.

Question 9

Answer 9

C

Question 10

Answer 10

E

Question 11

In regards to a reentrant loop, what will cause a reduce in duration of the AP?

Answer 11

Increase of I_K or decrease in I_CaL

Question 12

What is a normal extracellular potassium concentration?

Answer 12

3.5 to 5 mEq/liter

Question 13

What are the terms for increased and decreased extracellular potassium levels?

Answer 13

Hypokalemia - decreased

Hyperkalemia - increased

Question 14

What causes the resting depolarization associated with hyperkalemia?

Answer 14

A less negative E_K than normal

Question 15

What is the mechanism by which hypokalemia will produce a depolarizing resting membrane potential?

Answer 15

Hypokalemia reduces K conductance. Apparently, the effect on membrane potential produced by the reduction of K conductance more than offsets the effect of the more negative Nernst potential produced by hypokalemia. The depolarized resting potential in hypokalemia depresses membrane excitability similar to that occurring in hyperkalemia. The decreased K conductance slows phase 3 repolarization causing the T-wave to flatten and a U wave may appear.

Question 16

What is the mechanism by which EADs can occur?

Answer 16

EAD production occurs via conversion of inactive L-type calcium channels back to the active state during phase 2 or early phase 3 of the action potential. This reactivation can occur because there is a potential region where the Ca-channel activation and inactivation curves overlap. Decreased rate of repolarization (low I_K) markedly increases the chances of these because there is more time in the “calcium window”. This can allow Ca++ to move into the cell through those channels and create a depolarizing current and move V more positive.

Question 17

What effect will hypokalemia have on gK, IK, and action potential? What will hyperkalemia do?

Answer 17

Question 18

What two conditions make reentrant loops more likely?

Answer 18

Conduction velocity in decreased and duration of the AP is decreased.

Question 19

As potassium outside the cell increases what happens to E_K? What happens to E_K when potassium outside the cell decreases?

Answer 19

As K outside the cell increases, E_K becomes less negative and moves toward zero.

As K outside the cell decreases, E_K becomes more negative.

Question 20

What effect will hyper and hypokalemia have on the T wave of an ECG?

Answer 20

The T wave is the repolarization of the ventricles. This is largely dependent on potassium. Hypokalemia will have a reduced current thus causing the T wave to look flat and prolonged. Hyperkalemia will have the opposite effect and the T wave will appear shorter and spiked.

Question 21

Answer 21

C

Question 22

How will ischemia affect action potential generation?

Answer 22

Ischemia (insufficient blood flow) will lower O2 levels in the heart and decrease ATP formation. The mechanism is similar to hypoxia, but the decreased blood flow will allow K+ to accumulate which will result in local hyperkalemia. This will cause a depolarization of resting membrane potential, phase 4 of resting membrane potential will be more positive.

Question 23

What would be the effect of hyperkalemia on E_K in a cell?

Answer 23

There would be a reduced chemical force driving K+ out of the cell as compared to normal. The electrical force needed to balance the reduced chemical force will be less than under normal conditions. Therefore, the Nernst potential will be less negative or more positive than under normal conditions

Question 24

Increasing the membrane potential would have what effect on the number of sodium activation gate needed to open to hit the threshold value?

Answer 24

There would need to be and increased number of activation gates open in order to achieve the threshold value. This is due to the threshold value being more positive.

Question 25

What is the formula for changes in potassium current?

Answer 25

Question 26

What can occur due to a suppression of K+ current?

Answer 26

Early after depolarizations

Question 27

Answer 27

C

Question 28

The negative shift in MDP acts to do what on the heart?

Answer 28

This negative shift in MDP acts to slow heart rate by increasing the potential difference between MDP and the threshold for activation of the L-type calcium current

Question 29

What are the mechanisms by which decreased potassium current will speed up the heart?

Answer 29

The decreased conductance causes MDP to become more positive even though EK becomes more negative. In addition, the decreased K conductance allows the **funny sodium current to be more effective at driving phase 4 depolarization which results in a faster phase 4 depolarization.**

Question 30

How do treat hypokalemia? While treating hypokalemia what will you notice on a patients ECG?

Answer 30

Slow infusion of potassium in order to not overshoot the needed K level. While correcting the hypokalemia you would notice the T wave become shorter and the U wave would disappear.

Question 31

Why do normal people tend to not have problems with EADs?

Answer 31

Normally the ventricle repolarizes quickly enough through the calcium window that activation gates close before there is enough time for inactivation gates to open.

Question 32

What are the three things required for a reentrant loop?

Answer 32

Question 33

Is a U wave characteristic of hyper of hypokalemia?

Answer 33

Hypokalemia

Question 34

Answer 34

D

Question 35

How can cocaine increase a person's chances for an EAD?

Answer 35

Cocaine blocks delayed rectifier K channels, slowing the rate of repolarization, and impairs the reuptake of norepinephrine by SYM nerves (increases Ca++ window)

Question 36

What are four important outcomes when I_Na is decreased?

Answer 36

Threshold potential becomes more positive - decreased excitability Rate of rise in an action potential would be decreased Amplitude of action potential will be decreased (diminished height of QRS complex on ECG) Decreased conduction velocity (Resulting in wide P wave and wide QRS complex on ECG)

Question 37

Hyper and hypokalemia both cause depolarization of resting membrane potential. What would this effect be on the number of resting Na⁺ channels and the I_Na?

Answer 37

This would decrease the number of resting Na channels thus decreasing the I_Na during the upstroke of the action potential

Question 38

In regards to a reentrant loop what will cause a decrease in conduction velocity?

Answer 38

Decrease I_Na

Question 39

How can Beta-adrenergic blockers treat Torsades de Pointes?

Answer 39

Potassium current would be decreased throughout the ventricles action potential would be prolonged and that could affect the reentrant loop.

Question 40

Why in this graph might the line for E_K be trending upwards?

Answer 40

Because as K_O increases E_K becomes less negative and moves towards zero.

Question 41

How does resting depolariztion of cardiac muscle during hyperkalemia affect resting calcium channels?

Answer 41

Question 42

What will the effect of hypo and hyperkalemia be on MDP (maxiumum diastolic potential)?

Answer 42

Hyper - decrease make more negative; phase 4 will be less steep; decreased rate of firing of the SA node Hypo - increase make more positive; phase 4 more steep; Tachycardia Phase 4 is in reference to an action potential

Question 43

What is flaccid paralysis and what is it a result of?

Answer 43

Potassium disturbances will reduce voltage-gated sodium current in nerve and skeletal muscle. This will result in a person experiencing difficulty contracting their limbs.

Question 44

How does sodium bicarbonate affect potassium regulation?

Answer 44

An increase in extracellular pH (as produced by infusing sodium bicarbonate) will enhance the movement of Na into the cell by the Na-H exchanger. **This is an indirect effect.**

Question 45

In hypokalemia, what is the major cause of resting depolarization?

Answer 45

Decreased g_K. This will lead to an increase fg_Na

Question 46

Answer 46

A

Question 47

Short QT syndrome can be caused by?

Answer 47

Increased potassium current

Question 48

What is the mechanism by which DADs can occur?

Answer 48

Elevated heart rates can cause an **accumulation of calcium within the myocytes** (because there is insufficient time to pump all Ca++ out of cell). sarcoplasmic reticulum. Normally these calcium sparks are of no consequence. However, when the sarcoplasmic reticulum becomes overloaded with calcium the intracellular calcium (most likely in microenvironments) can increase to the level that **activates a non-selective cation channel in the cell membrane.** At negative membrane potentials, **sodium ions will enter the cell providing an inward ionic current that can depolarize the cell**. Also, the increased calcium level will favor the movement of calcium out of the cell via the Na-Ca exchanger. Since the movement of a calcium ion out of the cell via the exchange also moves 3 sodium ions into the cell, a net inward current is produced by the exchanger. The inward current carried by the Na-Ca exchanger also contributes to DAD production.

Question 49

What will an increase in extracellular Ca levels do to excitability of nerve, skeletal muscle, and cardiac muscle in a person with normal extracellular K+ level?

Answer 49

This would shift Na inactivation and activation curves more positive. Since the person has normal K+ levels the positive shift in Na inactivation channels would have little effect on the number of resting Na+ channels. The positive shift in the Na+ activation curve would **shift the threshold to a more positive value and thus would cause reduced excitability in the person.**

Question 50

If enough myocytes are generating EADs or DADs, the depolarizing current could be sufficient enough to trigger what?

Answer 50

Reentrant loop

Question 51

How does succinyl choline affect potassium regulation?

Answer 51

The increased intracellular sodium will stimulate the Na-K pump and move potassium into the cell