EC coupling II

Question 1

What does the process calcium-dependent inactivation (CDI) mean?

Answer 1

The L-type Ca2+ channels undergoes a form of inactivation that depends on the [Ca2+] near the cytoplasmic side of the channel

(basically this means it depends on amt of Cs2+ entering through the L-type Ca2+ channel and the amount of Ca2+ released via RyR2)

Question 2

Norepinephrine released by sympathetic nerve terminals and circulating epinephrine act to do what 4 things?

Answer 2

1. Increase Heart Rate (positive chronotropy) by raising the firing rate of pacemaker cells in the SA node.
2. Alter propagation through the conduction pathways
3. Increase Contractile Force (positive inotropy)
4. Increase Rate of Relaxation (positive lusitropy)

Question 3

3. Increase Contractile Force (positive inotropy)
   and
4. Increase Rate of Relaxation (positive lusitropy)
   both require the activation of what 3 things?

Answer 3

• β-adrenergic receptors
• elevation of cytoplasmic cAMP
• activation of Protein Kinase A (PKA).

Question 4

Four important targets for PKA in myocardium are:

Answer 4

• The L-type Ca2+ channel
• RyR2
• Phospholamban (PLB)
• Troponin

Question 5

Phosphorylation of the L-type Ca2+ channel does what?

Answer 5

increases the amplitude of the L-type Ca2+ current

The increased Ca2+ entry also helps to increase the quantity of Ca2+ stored in the SR.

Question 6

Phosphorylation of RyR2 causes what?

Answer 6

causes it to be sensitized to activation by trigger Ca2+

Question 7

Phosphorylation of Phospholamban causes what?

Answer 7

causes PLB to dissociate from SERCA2 –> relieves the inhibition and thus INCREASES Ca2+ pumping into the SR.

This speeds relaxation and increases the quantity of Ca2+ stored in the SR

Question 8

Phosphorylation of troponin does what?

Answer 8

speeds the rate of Ca2+ dissociation from thin filaments.

Question 9

describe what phosphorylation of these things contribute to with regards to Inotropy and Lusitropy:

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

Answer 9

1. DHPR (L-type Ca2+ channel)
   
   • positive inotropy
2. RyR2
   
   • positive inotropy
3. PLB
   
   • positive inotropy and lusitropy
4. Troponin
   
   • positive lusitropy
     (speeds Ca2+ dissociation remember?)

Question 10

With regards to Relaxation: Rank the calcium channels in terms of getting rid of calcium.

Answer 10

SERCA > NCX > PMCA

SERCA: Pumps 2 Ca2+ per cycle
NCX: cleans up Ca2+ not removed by SERCA2 (Pumps 2 Ca2+ per cycle in either direction)
PMCA: plasma membrane calcium ATPase - moves calcium out of the cell
- 1 calcium per cycle

Question 11

calcium-dependent inactivation (CDI)

Answer 11

• If the amount of Ca2+ in the SR (and thus the amount released via RyR2) increases, greater CDI causes less Ca2+ to enter via the L-type channel.
  Converse is true:
• if there is decreased content of Ca2+ in the SR and decreased Ca2+ release via RyR2, then there is less CDI and greater Ca2+ entry via the L-type channel.
• Overall, CDI helps to maintain a constant SR Ca2+ content.