Cardiac contraction

Question 1

Structure of cardiomyocytes

Answer 1

60-140 μm in length and 17–25 μm diameter make up branching myofibres
Each myocyte contains myofibrils, composed of repeating sarcomeres

Question 2

What are T tubules?

Answer 2

Invaginations of the muscle cell membrane that penetrate the centre of cardiac muscle cells

Question 3

Function of T tubules?

Answer 3

Contain Ca+ channels and ensure that calcium is delivered deep into the cells, close to the sarcomere

Question 4

How does the calcium leave the cell?

Answer 4

Predominantly through an Na+/Ca2+ exchanger

Question 5

What determines contraction?

Answer 5

INCREASE in intracellular Ca+

Question 6

What determines force of contratction?

Answer 6

Amount of increase in Ca+

Question 7

Explain how Ca+ leave the cell/ decreases and how the the cells relax

Answer 7

1. Action potential repolarisation (K+ ions leave) repolarises T-tubules – closure of VGCCs, and less Ca2+ influx.
2. No Ca2+ influx, no CICR.
3. Extrusion of Ca2+ from cell (30%)- by Na+/Ca2+ exchanger.
4. Ca2+ uptake into sarcoplasmic reticulum (SR) via SR membrane Ca2+ATPase (around 70%).
5. Ca2+ in SR for next contraction, even relaxation requires energy (ATP).
   Uptake of Ca2+ in mitochondria.

Question 8

How does noreadrenaline increase contractility?

Answer 8

Acts on beta 1 receptors to increase contractility by phophorylating calcium channels and allowing greater Ca+ influx

Question 9

What are inotropes?

Answer 9

substance altering force/energy of muscle contractions

Question 10

What does increases PKA lead to?

Answer 10

1. Increased Ca2+ channel so higher Ca2+ levels and greater contraction.
2. Increased sarcoplasmic reticulum Ca2+ATPase, so uptake of Ca2+ into storage by SR allowing faster relaxation.
3. Increased K+ channel opening so faster repolarisation and shorter action potential, leads to faster heart rate.
4. Overall stronger faster contractions but same diastolic time to allow for filling with blood & coronary perfusion.

Question 11

Name two types of positive inotropes and how they work

Answer 11

1. Increasing voltage gated calcium channel activity (sympathetic mimetic)
2. Reducing Ca2+ extrusion (cardiac glycosides)

Question 12

What is digoxin?

Answer 12

Digoxin is a cardiac glycoside (reduces Ca+ extrusion)
Used to treat chronic heart faliure
Not used so much now due to side effects

Question 13

Describe the mechanism of action by which digoxin works?

Answer 13

1. Digoxin inhibits Na+/K+ ATPase.
2. Build up of intracellular Na+ lowers concentration gradient (which normally powers Na+/Ca2+ exchanger).
3. Less Ca2+ expulsion by Na+/Ca2+ exchanger.
4. More Ca2+ uptake into stores and greater CICR.

Question 14

Name some other inotropic agents

Answer 14

Dobutamine
Dopamine
Glucagon
Amrinone