arrhythmia mechanism 2

Question 1

antiarrhythmic drugs should be selected based on the

Answer 1

specific molecular basis of long QT syndrome.

Question 2

For patients with the LQT3 mutations, use:

Answer 2

drugs that block Na+ channels

Question 3

for patients with LQT1 or LQT2 mutations, use:

Answer 3

drugs that open K+ channels ought to be used

Question 4

effects of Ina

Answer 4

incomplete Ina inactiation

Question 5

effects of Ica-L

Answer 5

incomplete Ica inactivation

autism (timothy syndrome)

Question 6

effects of Ikr

Answer 6

decrease in K+ current

Question 7

effects of Iks

Answer 7

decrease in K+ current

Question 8

effects of Ik1

Answer 8

decrease in K+ current (during diastole)

Question 9

Brugada syndrome

Answer 9

1. congenital arrythmia

2. ventricular fibrillation results in a survival rate of only 40% by 5 years of age.

Question 10

finnish familial arrhythmia mechanism

Answer 10

1, The protein yotiao binds protein kinase A, cardiac Ca2+ channels and K+ channels Yotiao thus anchors this kinase to cardiac Ca2+ and IKS channels

2. A mutation in IKS channels prevents yotiao binding to this channel
3. The mutant K+ is not properly upregulated by β receptor activity

Question 11

In finnish familial arrythmia, yotiao mutation leads to

Answer 11

1. during ↑ sympathetic activity (exercise, emotion),
2. not enough repolarizing K+ current to match the increased depolarizing Ca2+ current.
3. Phase 2 is prolonged, cytosolic Ca2+ levels rise, triggering afterdepolarizations and arrhythmia.

Question 12

two types of problems in arrhythmia:

Answer 12

(1) inappropriate impulse initiation in SA node or elsewhere (ectopic focus), and
(2) disturbed impulse conduction in nodes, conduction cells (Purkinje cells) or myocytes.

Question 13

Inappropriate impulse initiation - identified by

Answer 13

abnormally depolarized diastolic membrane potential

Question 14

Inappropriate impulse initiation - caused by

Answer 14

1. ectopic foci

2. triggered afterdepolarizations

Question 15

ectopic foci:

Answer 15

because normal SA nodal pacemaker is abnormally slow, or ectopic focus is abnormally fast infarct - causes membrane to depolarize

(decrease in [K+]i occurs as Na/K-ATPase fails)

Question 16

early afterdepolarizations (EADs):

Answer 16

1. appear during late phase 2 and phase 3
2. largely dependent upon re-activation of Ca2+ channels in response to elevated [Ca2+]in prolongation of phase 2 (long QT) contributes to elevated [Ca2+]in

Question 17

delayed afterdepolarizations (DADs):

Answer 17

1. during early phase 4
2. initiated by elevated [Ca2+]in and, consequently, elevated Na+/Ca2+ exchange
3. the Na+/Ca2+ exchanger is electrogenic: 3 Na+ move in for 1 Ca2+ moved out
4. net increase in positive charge inside myocytes corresponds to depolarization this exchanger is called NCX, and the current it generates is INCX

Question 18

Prolonged phase 2

INCX will cause

Answer 18

excess Ca2+ entry, which triggers excess Ca2+ release from SR.
Elevated [Ca2+]in drives increased Na/Ca exchange via the NCX exchanger.

Question 19

Prolongation of QT interval leads to

Answer 19

early afterdepolarizations and arrhythmia.

Question 20

Disturbed impulse conduction: Will cause:

Answer 20

1. conduction block

2. re-entry

Question 21

Re-entry underlies:

Answer 21

1. atrial flutter and fibrillation,
2. torsades de pointes and
3. ventricular fibrillation.