Heart Lecture 6: Myocardial Excitation - Contraction Coupling

Question 1

What triggers Ca++ release from the SR in skeletal muscle?

Answer 1

voltage (electrical activity carried down sarcolemma via T-tubules)

Question 2

What triggers Ca++ release from the SR in cardiac muscle?

Answer 2

Ca++ influx through voltage gated Ca++ channels

Question 3

What keeps Ca++ concentrations high in the sarcoplasmic reticulum?

Answer 3

SERCA (sarcoplasmic and endoplasmic reticulum Ca++ ATPase)

Question 4

What does SERCA do?

Answer 4

pump calcium from the cytosol back into the sarcoplasmic reticulum

Question 5

What inhibits SERCA?

Answer 5

Phospholamban

Question 6

What happens to phospholamban when it is phosphorylated?

Answer 6

It is inhibited therefore releasing its inhibition on SERCA, allowing calcium to return to the SR

Question 7

What two things regulate calcium in the cytosol?

Answer 7

1) Ca++ influx into the cell

2) Ca++ in the SR

Question 8

What is the molecular problem in congestive failure?

Answer 8

poor calcium handling

Question 9

What effect do catecholamines have on muscle?

Answer 9

increase adenylyl cyclase activity which makes cAMP

cAMP activates PKA which phosphorylates phospholamban allowing Ca++ uptake in the SR (enhances/speeds up relaxation)

PKA also phosphorylates Ca++ channels to increase Ca++ influx

Question 10

Sympathetic has what influence on the heart?

Answer 10

Increases strength of contraction and heart rate

Question 11

What do cardiac glycosides do?

Answer 11

1) inhibit Na,K-ATPase
2) inhibit intracellular [Na] thereby decreasing [Na] gradient
3) decreases Ca++ extrusion via Na-Ca exchanger and increases intracellular [Ca]
4) increase in SR Ca++ content leading to greater SR Ca++ release and contraction