Lecture 3

Question 1

What does the heart need to do in order to contract mechanically?

Answer 1

It needs to be activated electrically. In an organized sequence, you get a coordinated contraction of different parts of the heart.

Question 2

what are the properties of myocytes in the heart?

Answer 2

1) Excitability - cardiac cells have an action potential (AP).
2) Conductivity -
3) Automaticity -

Question 3

What is the duration of an AP in the heart?

Answer 3

200-300msec.

Question 4

Describe a fast response AP-phase?

Answer 4

Most of the working muscle cells in the heart have fast response AP.

4) Resting potential -80mV. The only channels that are open are potassium channels. Thus the membrane potential is set by Potassium concentration gradient.
0) Rapid upstroke - the depolarization which is very rapid. Sodium channels once we reach the threshold for sodium (-70mV). The driving force for sodium is very high. The concentration gradient for sodium is inwards, the electrical gradient is inwards as well. Both components of the electrochemical gradient for sodium are pushing sodium into the cell (rapid influx and rapid depolarization). These channels open and shift very rapidly, this tells us that they are voltage dependent but time dependent as well.
1) Small repolarization - some channels (potassium channels - current into which is dependent on potassium). The current switches on then off again.
2) Plateau - the sodium channels have shut (are in refractory). There is inward going current and outward going current. If there is current travelling across, but no potential, then the net current is around 0. The potassium current (iK1) is still open and conducting. The sodium/calcium exchanger is still occurring (inward going current). There is no change in potential.
3) Rapid repolarization - the potassium channels that determine this repolarization are the focus of a lot of drugs. when it opens potassium current moves outwards, it is delayed. It is told to turn on by a potential change, however it is time dependent, so there is a delay before the channels open. the outward current now starts to repolarize the cell. The iK1 channels sense the reducing voltage.
4) Resting potential.

The AP shape is determined by the different ion channels that are opening and closing across the membrane.

Question 5

Describe the timing of ionic currents (potassium)?

Answer 5

There is always outward going current. The current increases and decreases.

Question 6

Describe slow response AP-phases?

Answer 6

The upstroke is not as rapid as the fast response. The cells when they conduct, don’t conduct as rapidly due to the currents not being as intense. In some cases it is useful and in some cases it is a problem. The upstroke is due to the calcium current. Depolarisation of the threshold opens calcium channels, influx of calcium, but not as intense as the sodium channels. The sodium channels are already open at this potential. The resting potential is not as negative as the fast response.

You find slow response AP cells in the AV node and SA node. However they can potentially be pace-making cells in these areas.

Question 7

Describe excitability?

Answer 7

Refractory period is important for the mechanical function of the heart and for the generation of arthymias.

Question 8

Describe the absolute refractory period?

Answer 8

You cannot stimulate a group of cells during this period. This is essential for cardiac function. It means you can’t tetanize the heart. The heart has to contract to eject blood, but it needs to be relaxed in order to fill.

Question 9

Describe the relative refractory period?

Answer 9

Can generate an AP if you use a higher than normal stimulus. But the AP won’t be a full one, it will be poor and slowly conducting. Can generate arythmias.

Question 10

Describe the super normal period?

Answer 10

Can stimulate AP with a smaller than normal stimulus. AP are slowly conducting and not normal.

Question 11

Describe conductivity?

Answer 11

Skeletal muscle is neurogenic. every cell is connected to a nerve, and it only contracts when the nerve sends an AP. The heart is myogenic, you do not need nerves to the heart. Myogenic activation originates within the heart, and activation spreads from cell to cell (each cell is connected via nexus junctions).

Question 12

Describe automaticity?

Answer 12

There are pacemakers in the heart, that fire off on their own accord. SA node and some cells in the AV node and the purkinje fibers. the fastest pacemaker controls the automaticity, if that dies then the next fast pacemaker cell takes over.

Question 13

Describe pacemaker AP-phases?

Answer 13

There is a resting phase that is slowly depolarizing. The steepness of the line depends on inward and outward going current. The steeper the line = the greater the difference between outward and inward current. the outward currents are potassium, and the inward current is calcium and if (sodium current - funny current due to the current that turned on when you hyperpolarized the cell).

Question 14

Describe the three theoretical ways to change heart rate?

Answer 14

1) Increase or decrease the slope, can reach threshold at a different time - thus speed up or slow down the heart rate. To change the slope you increase or decrease inward/outward-going current depending on what you want to do.
2) Increase or decrease the level to which this potential goes before it starts up again. If we hyperpolarize the cell it will take longer to reach threshold. Can change the minimum diastolic potential.
3) Changing the threshold potential (potential on which an AP is generated).

Question 15

How does our body change heart rate?

Answer 15

Use the autonomic nervous system. The PNS slows heart rate (main regulator of rate). If we increase the PNS - release ACh, there are potassium channels in the heart called iKACh (open when ACh is around). This will have an increase in outward going current, reduce the slope and have hyperpolarisation of the membrane.
SNS - phosphorylate calcium channel, this can generate longer opening therefore calcium inward current, thus faster depolarisation (faster upstroke).

Question 16

Describe the ranges of heart rate?

Answer 16

Normal = 60-100bpm.
Bradycardia = 100bpm.

Question 17

Describe the activation of the heart?

Answer 17

The timing of each component, tells us when each different path depolarises in the cardiac cycle. The ECG is a sum of the AP.

Question 18

Describe the activation pathway?

Answer 18

Start off in the SA node (at base of SVC). Cells are continuous with atrial myocardium. There are special properties around the SA node that allow the conduction to spread. There are tracks that go across of the atria to speed up activation. Activation spreads through the atria. The ventricles in the atria are isolated electrically - the CT barrier (valve rings) this except for the AV node and a bundle of muscle going down into the ventricles (inter-septum holding the bundle of His). Then get into the Bundle of His (fast conducting specialised conduction system). You then divide into right and left bundle branches (one on each side of the septum). The bundles split into purkinje fibres (fast/very rapid conducting fibres - spread out and cover entire endocardial surface of both ventricles. Activation spreads from the inside surface of the ventricles out across the ventricular wall - activation is coordinated. Important that the sequence of activation is followed very carefully.

Question 19

What is the AV node’s job?

Answer 19

Slow upstroke AP/delay conduction of the ventricles. Want the atria to contract, to allow the ventricles to fill (20%) before the ventricles contract.

Question 20

Describe the SA node importance as the pacemaker for the heart?

Answer 20

The SA node is the pacemaker for the heart, as it is functioning at the highest rate. It manages to dominate as it suppresses the other pacemakers (overdrive suppression). Pacemaker that you force to go at a rate faster than it’s expecting to, will suppress its rate even more. You have more inward going sodium current (as more AP) that has to be pumped out by Na+/K+/ATPase (electrogenic - hyperpolarise a cell, take longer before it gets to next AP). If you turn off the suppressor they will pacemaker at a slightly higher rate than what they are doing currently.

Question 21

Describe why AV block can occur in the AV node?

Answer 21

Because it is slow conducting, it is subject to block (AV block). Occur at the AV node due to the particular properties that the AV node needs to have to cause delay of signal.

Question 22

Describe the determinants of conduction velocity?

Answer 22

Conduction rate depends on a number things:

1) Radius of the cells, due to the amount of resistance. the bigger the cross-sectional area the smaller resistance.
2) Amplitude of AP - fast upstroke correlates with high conduction velocity.
3) Intensity of the current.

Velocity is proportional to the square root of the radius of the cell.

Question 23

Describe Wolff-Parkinson-White Syndrome?

Answer 23

Due to an abnormal electrical pathway between atria and ventricles. When activation starts at the SA nodes and spreads through the atria, before it gets into the ventricle through the AV node it gets into them through the extra bundle. Most of the time, it looks perfectly normal except for a funny thing on the ECG. Collapsing is due to one of the pathway for that particular beat didn’t conduct. Came back up and stimulated the muscle before the SA node had a chance (re-entrant pathway). get an increased HR (tachycardia). Macro-re-entrance circuit that generates high heart rate.

Question 24

How do you fix WPW syndrome?

Answer 24

Disconnect the extra bundle. Allows us to draw activation maps to see where the activation spreads. This will tell us the location of the pathway. The surgeon will use the map. Can put catheters into the RA, and on the end is an electrode that’s measuring activation. Find the point where there is early activation round the AV ring (around the coronary sinus). You will put energy into that location (radio frequency, cold or hot) and burn at the tip and burn the pathway.