Myocardial Excitation-Contraction Coupling

Question 1

What is the sarcolemma?

Answer 1

Controls Ca2+ influx via the slow inward Ca2+ current

Question 2

What are the T tubules?

Answer 2

Transmits electrical activity to cell interior

Question 3

What is troponin C?

Answer 3

Ca2+ receptor on actin filaments

Question 4

What are the terminal cisternae?

Answer 4

Part of the SR

Ca2+ influx triggers the Ca2+ release for contraction here

Question 5

What are the longitudinal cisternae?

Answer 5

Part of the SR

Ca2+ uptake site for relaxation

Question 6

Describe the cardiac EC coupling pathway.

Answer 6

Action potential -> 
T tubules ->
Depolarization leads to Ca2+ influx ->
Ca2+ binds to RyR ->
Release of Ca2+ from SR ->
Ca2+ binds troponin C ->
Contraction

Question 7

Describe the relaxation phase of cardiac EC coupling.

Answer 7

After contraction ->
SR Ca2+ uptake ->
Na/Ca exchange ->
Sarcolemmal Ca2+ pump ->
Relaxation

Question 8

What is the difference in skeletal and cardiac EC coupling?

Answer 8

Cardiac muscle contraction is dependent on Ca influx but skeletal muscle is not. Skeletal muscle is dependent on physical conformation changes in the DHPR.

Skeletal muscle is also mostly anaerobic while cardiac muscle is aerobic. Lastly, skeletal muscle has high compliance whereas cardiac muscle does not.

Question 9

What are catecholamines and their inotropic effect?

Answer 9

They are NE and E and are positive inotropic agents.

Question 10

How do catecholamines work?

Answer 10

Bind beta receptors which activates adenylyl cyclase and increases cAMP which activates PKA. PKA phosphrylates phospholamban which increases Ca2+ uptake into the SR -> increased relaxation rate.

Question 11

What are cardiac glycosides and their inotropic effect?

Answer 11

Digitalis and they have a positive inotropic effect used in heart failure.

Question 12

How do cardiac glycosides work?

Answer 12

Inhibit the Na/K pump, which increases in the intracellular [Na+]. This interferes with the Na/Ca pump so intracellular [Ca2+] increases.

The high [Ca2+] leads to greater SR Ca2+ release and stronger contractions.

Question 13

What are Ca2+ channel blockers and their inotropic effect?

Answer 13

Verapimil and they have a side effect of negative inotropic effect.

Question 14

How do Ca2+ channel blockers work?

Answer 14

They are used as anti-arrhythmia agents and they block the Ca2+ influx which inhibits the action of the AV node AP and blocks things like SVT.

Ca2+ influx blocks decreases the [Ca2+] in the cell which decreases contraction strength of the heart as a side effect.

Question 15

What is a positive staircase and how does it work?

Answer 15

Contraction strength increases as HR increases. This is due to the greater Ca2+ influx per unit time and less time for the efflux of Ca2+.

Question 16

What is a negative staircase and how does it work?

Answer 16

As HR decreases, contraction strength also decreases. This is due to less Ca2+ influx per unit time and more time for Ca2+ efflux.

Question 17

What are premature beats and what is the cause?

Answer 17

They are earlier and smaller than normal contractions. They are caused by the early AP occurring which means less time for Ca current recovery and less time for SR Ca2+ recovery. There is smaller Ca-induced Ca-release so the contraction strength is weaker as a result.

Question 18

What are post-extrasystolic potentiations and what is the cause?

Answer 18

They are stronger than normal contractions following a premature beat. They are caused because there is more time for the recovery of Ca current and more time for the recovery of SR Ca2+ release channels.

Question 19

What is the function of phospholamban?

Answer 19

It normally inhibits the SERCA Ca2+ recovery pump, but when it is Pi, it will increase Ca2+ uptake into the SR.

Question 20

How do beta receptors influence the heart?

Answer 20

Beta receptors activate the cAMP -> PKA -> Troponin I -> Binding of Troponin C by Ca

They also increase the relaxation rate of the heart.