EXAM #1: MECHANISMS OF DYSRHYTHMIAS

Question 1

What phases of the cardiac myocyte action potential correspond to the absolute refractive period?

Answer 1

0, 1, and 2

Question 2

What phase of the cardiac myocyte action potential corresponds to the relative refractive period?

Answer 2

3

Question 3

What are the two important parts of the Na+ channel related to the refractory periods?

Answer 3

1) Inner pore

2) Inactivation gate

Question 4

What is the conformational state of the Na+ channel during the resting membrane potential?

Answer 4

• Inner pore is closed

- Inactivation gate is open

Question 5

What happens to the confirmation of the Na+ channel during depolarization?

Answer 5

Depolarization= conformational change that OPENS the inner pore

Question 6

After depolarization, what causes the inactivation gate to plug the Na+ channel?

Answer 6

Time after depolarization

Question 7

What is the outcome of the Na+ channel being plugged with the inactivation gate?

Answer 7

Absolute refractory period

Question 8

What causes the inactivation gate to unplug the Na+ channel?

Answer 8

More time

Question 9

How does the relative refractory period relate to the inactivation gate?

Answer 9

• The inactivation gate is in the process of moving out of the way
• STRONG impulse CAN cause an action potential

Question 10

What effect does a Na+ channel blocker have on the cardiac action potential?

Answer 10

Prolongs the absolute refractory period

Question 11

What is excitation contraction coupling?

Answer 11

Coupling of electrical stimulus with mechanical contraction

Question 12

How does excitation-contraction coupling in cardiac muscle compare to skeletal muscle?

Answer 12

Time delay= ~150 m/sec, which is MUCH LONGER than skeletal muscle

Question 13

Outline excitation-contraction coupling in cardiac muscle cells to cause contraction.

Answer 13

1) Depolarization opens voltage-gated Ca++ channels
2) Ca++ influx
3) Ca++ binds RyR on SR
4) Ca++ induced Ca++ release from the SR
5) Ca++ binds troponin

Contractile shortening of the sarcomere occurs

Question 14

Outline relaxation in cardiac muscle cells.

Answer 14

1) Ca++ dissociates from Troponin
2) Ca++ is taken up into SR via SERCA (SR Ca++ pump)
3) Ca++ binds proteins in SR e.g. calsequestrin
4) Ca++ is pumped OUT via
- Na+/Ca++ exchanger
- Ca++ pump

Question 15

What is the difference between Ca++ handing in skeletal and cardiac muscle cells?

Answer 15

• In SKELETAL m. Ca++ channel is in CONTACT with RyR

- In CARDIAC m. Ca++ influxes into the cell, THEN binds with RyR on SR for Ca++ release

Question 16

Generally, what is the stimulus for contraction of a cardiac myocyte? Relaxation?

Answer 16

Intracellular Ca++= contraction

Lack of intracellular Ca++= relaxation

Question 17

What is one element of the pathology of HF that underlies contractile impairment?

Answer 17

Limited Ca++ influx= less Ca++ induced Ca++ release

–>Less cardiac contractility

Question 18

Generally, what is an active arrhythmia?

Answer 18

Change in automaticity

- E.g. nodal cells w/ phase 4 depolariztion

Question 19

What happens in the SA node for sinus brady and tachycardia?

Answer 19

Tachycardia= increased slope of diastolic phase 4 depolarization

Bradycardia= decreased slope of diastolic phase 4 depolarization

Question 20

How does sympathetic stimulation increase HR?

Answer 20

1) Activating HCN (funny current)

2) Increasing Ca++ influx

Question 21

How does parasympathetic stimulation decrease HR?

Answer 21

1) ACh
2) ACh causes INCREASED K+ current

–>Decreased phase 4 depolarization

Question 22

What are the types of triggered arrhythmogenesis?

Answer 22

Delayed After Depolarization

Early After Depolarization

Question 23

What is a delayed after depolarization (DAD)? EAD?

Answer 23

DAD= arrhythmia generated during phase 4 
EAD= arrhythmia generated during phase 2 or 3

Question 24

What causes DADs?

Answer 24

Increased Ca++, which can be either:

• Cytosolic
• SR

Question 25

What causes EADs?

Answer 25

• Altered ion flux during plateau phase of AP

- Characterized by extended APD

Question 26

List mechanisms that will prolong the APD.

Answer 26

1) Reduced K+ current opposing Ca++
2) Increased Ca++ opposing K+
3) Increased Na+/Ca++ exchange activity
4) Increased late Na+ current

Question 27

Why can EADs be exacerbated by low HR?

Answer 27

APD is already long in low HR

Question 28

List the mechanisms that will lead to DADs.

Answer 28

1) Mutation in Ca++ binding proteins
- Calsequestrin
- SERCA
2) High HR

Question 29

Why are DADs exacerbated by high heart rates?

Answer 29

• Short APD

- Less time for Ca++ sequestration/ cycling

Question 30

What is a reentrant circuit?

Answer 30

Impulse travels via an accessory pathway in the conduction system

Question 31

List the examples of re-entrant circuits.

Answer 31

1) WPW
2) AVNRT
3) A-flutter
4) PSVT

Question 32

How is anatomical re-entry treated?

Answer 32

Ablation

Question 33

What is a functional re-entry circuit?

Answer 33

• Absence of a defined anatomical pathway
• Spatial or electrical differences between cells generate difference in conduction

E.g. from ischemia or infarction

Question 34

What are examples of functional re-entry?

Answer 34

1) Monomorphic VT

2) Polymorphic VT/VF

Question 35

What does circus movement re-entry rely on?

Answer 35

Unidirectional block of conduction