coupling 2

Question 1

Four important targets for PKA in cardiomyocytes are:

Answer 1

1. The L-type Ca2+ channel
2. RyR2
3. Phospholamban (PLB)
4. Troponin

Question 2

calcium-dependent inactivation (CDI).

Answer 2

the L-type Ca2+ channel undergoes a form of inactivation that depends on the concentration of Ca2+ near the cytoplasmic side of the channel

Question 3

CDI depends on

Answer 3

on Ca2+ entering through the channel but also, to a large extent, on Ca2+ released via RyR2.

Question 4

if the amount of Ca2+ in the SR (and thus the amount released via RyR2) increases, what is the effect on CDI?

Answer 4

greater CDI causes less Ca2+ to enter via the L-type channel.

Question 5

decreased content of Ca2+ in the SR and decreased Ca2+ release via RyR2, what is the effect on CDI?

Answer 5

then there is less CDI and greater Ca2+ entry via the L-type channel.

Question 6

CDI helps to maintain a

Answer 6

constant SR Ca2+ content.

Question 7

Phosphorylation of the L type Ca channel

Answer 7

increases the amplitude of the L-type Ca2+ current, increasing

(1) the trigger for activation of RyR2 and over time
(2) the SR Ca2+ content.

Question 8

Phosphorylation of RyR2 results in an

Answer 8

increases its activation by Ca2+.

Question 9

PLB inhibits:

Answer 9

SERCA2 Ca2+ pumping activity;

Question 10

Phosphorylation of Troponin, results in

Answer 10

speeds Ca2+ off rate.

Question 11

phosphorylation of PLB

Answer 11

1. causes PLB to dissociate from SERCA2
2. increases Ca2+ pumping into the SR
3. which speeds relaxation and increases SR Ca2+ content.

Question 12

contributions to positive inotropy?

Answer 12

1. phophorylation of L type Ca channel

2. phosphorylation of RyR2

Question 13

contributions to positive inotrpy AND positive lusitropy?

Answer 13

phosphorylation of PLB

Question 14

contributions to positive lusitropy?

Answer 14

phosphorylation of troponin

Question 15

Difficulty in linking altered phenotype to altered genotype arises because studying the altered protein almost always requires a

Answer 15

model system.

Question 16

Timothy Syndrome is a

Answer 16

Genetic disorder resulting in cardiac arrhythmias.

Other frequent symptoms include immune deficiency and cognitive abnormalities.

Question 17

TS2 mutations profoundly suppress

Answer 17

voltage-dependent inactivation

Question 18

TS and TS2 patients display

Answer 18

1. AV block,
2. prolonged Q-T intervals (indicative of a prolonged ventricular action potential)
3. episodes of polymorphic ventricular tachycardia.