Electrical and Molecular Events in the Heart and Vasculature

Question 1

How is the resting membrane potential set up in the heart and whats its value?

Answer 1

Cell membrane permeable to K+ which move out of the cell. This leaves the net charge in the cell more negative than outside. RMP is -90 to -85mV

Question 2

Outline ventricular myocyte action potentials.

Answer 2

0 Voltage gated sodium channels open- steep rise in MP

1 Transient K+ efflux- initual repolarisation phase

2 Opening of L type voltage gated Ca2+ channels, calcium moves in and action potential plataeu.

3 Ca2+ channel inactivation so only K+ effluxing.

4 Return to RMP

Question 3

Outline a SAN action potential

Answer 3

Pacemaker potential rather than a resting potential at its most negative is -60mV. Slow depolarisation from Na+ influx through HCN. This makes it have natural automaticity.
Voltage gated Ca2+ channels open causing depolarisation at 600ms.
Voltage gated K+ ions open to repolarise to -60mV at 700ms.

Question 4

What happens in hyperkalaemia to the AP?

Answer 4

High K+ means more positive RMP, inactivation of Na+ channels - slower upstroke. The action potential also narrows

ECG- BIG POT=HIGH TEA (hyperK gives big T wave)

Question 5

What happens in hypokalaemia?

Answer 5

Lengthened action potential. Potassium increase outside cell so slower movement out in depolarisation. Risks early after depolarisations and VF.

Question 6

Describe the mechanism of cardiac cell contractions.

Answer 6

Cardiac myocytes are electrically active.

Excitation contraction coupling and sliding filament theory.

Question 7

Describe smooth muscle cell contraction

Answer 7

adrenaline/ noradrenaline binds alpha 1 receptor. Gq receptor.
PIP2—>IP3 +DAG
IP3 bind ryanidine receptor on SER and releases calcium.
DAG activates PKC which inhibits Myosin Light Chain phosphotase.
VGCC open from depolarisation. Calcium enters cell and binds calmodulin.
Calcium bound calmodulin activates myosin Light Chain kinase. Myosin phosphorylated which permits interactions with actin. Increased phosphorylation of myosin heads.
Contraction

Question 8

Is the action potential wake form different across the heart, e.g. he atrial muscle when compared to parking fibres?

Answer 8

Yes waveforms vary though out the heart.
SAN and AV node resemble each other but are not the same.
Atrial Purkinje and ventricle resemble each other but are not the same.

Question 9

What happens if action potentials fail to fire in the heart?

Answer 9

Asystole

Question 10

If action potentials fire too quickly what results?

Answer 10

Bradycardia

Question 11

No coordination in action potentials in the ventricles gives rise to what rhythm?

Answer 11

Ventricular fibrilation

Question 12

What plasma potassium is considered hyperkalaemic?

Answer 12

> 5.5mmol/L

Question 13

<3.5mmol/L potassium in the blood is considered to be…

Answer 13

hypokalaemia

Question 14

Why are cardiac cells so sensitive to potassium levels, even more than neurons?

Answer 14

The RMP of the ventricular myocytes is dependent on K+ movement. The RMP is closer to Ek for potassium in the heart than in nerves so must be more dependent on K+.

Question 15

What can happen in hyperkalaemia?

Answer 15

Increased excitability initially

Asystole

Question 16

What determines how the heart reacts to hyperkalaemia?

Answer 16

The timing of the onset- sudden or gradual

Question 17

5.5-5.9mmol/L K+ is ….. hyperkalaemia

Answer 17

Mild

Question 18

What is the plasma level above which a patient is considered to have sever hyper kalaemia?

Answer 18

6.5mmol/L

Question 19

What is the plasma level above which a patient is considered to have severe hyperkalaemia?

Answer 19

6.5mmol/L

Question 20

List treatments for hyperkalaemia.

Answer 20

Calcium gluconate - reduces excitability of the heart

Insulin and glucose - promotes cellular intake of K+ (ATP sensitive K+ channels)

Question 21

If the heart has stopped what do you give?

Answer 21

Adrenaline

Question 22

List treatments for hyperkalaemia if the heart is still beating.

Answer 22

Calcium gluconate - reduces excitability of the heart

Insulin and glucose - promotes cellular intake of K+ (ATP sensitive K+ channels)

Question 23

What is excitation contraction coupling?

Answer 23

Depolarisation opens L type calcium channels in T tubules.
Calcium induced calcium release from SER.
25% increase Ca2+ is from the plasma membrane and the rest from the SER.

Question 24

What is excitation contraction coupling?

Answer 24

Depolarisation opens L type calcium channels in T tubules.
Calcium induced calcium release from SER.
25% increase Ca2+ is from the plasma membrane and the rest from the SER.
Calcium binds Troponin C causing a conformational change which displaces tropomyosin from the myosin binding sites on the actin which allows the two proteins to interact.

Question 25

Which calcium pumps are important in retuning intracellular calcium levels in a cell to normal as the muscle cell relaxes?

Answer 25

SERCA (mainly)
PMCA
Na+/Ca2+ exchanger

Question 26

Which vessels have smooth muscle?

Answer 26

Arteries, arterioles and veins.

Question 27

Which vessels have smooth muscle?

Answer 27

Arteries, arterioles and veins.

Question 28

Which layer of a vessel wall contains smooth muscle?

Answer 28

Tunica media

Question 29

What allows smooth muscle in vessel walls to relax?

Answer 29

Ca2+ level in the cell drops. Myosin light chain phosphotase activity increases. This takes phosphates off myosin heads so they can no longer interact with actin.

Question 30

What happens if PKA phosphorylates MLCK?

Answer 30

Enzyme inhibited so no myosin phosphorylation.