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Flashcards in coupling 2 Deck (18):
1

Four important targets for PKA in cardiomyocytes are:

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

2

calcium-dependent inactivation (CDI).

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

3

CDI depends on

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

4

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

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

5

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

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

6

CDI helps to maintain a

constant SR Ca2+ content.

7

Phosphorylation of the L type Ca channel

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.

8

Phosphorylation of RyR2 results in an

increases its activation by Ca2+.

9

PLB inhibits:

SERCA2 Ca2+ pumping activity;

10

Phosphorylation of Troponin, results in

speeds Ca2+ off rate.

11

phosphorylation of PLB

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

12

contributions to positive inotropy?

1. phophorylation of L type Ca channel
2. phosphorylation of RyR2

13

contributions to positive inotrpy AND positive lusitropy?

phosphorylation of PLB

14

contributions to positive lusitropy?

phosphorylation of troponin

15

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

model system.

16

Timothy Syndrome is a

Genetic disorder resulting in cardiac arrhythmias.

Other frequent symptoms include immune deficiency and cognitive abnormalities.

17

TS2 mutations profoundly suppress

voltage-dependent inactivation

18

TS and TS2 patients display

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