Lecture 2: Electrical function of the heart (2021)

Question 1

What are the three electrical properties of a myocyte?

Answer 1

1) Excitability - AP’s
2) Conductivity - Cell-cell spread of electrical activity
3) Automacity- Intrinsic pacemaker activity.

(Co-ordinated electrical activation and thus contraction rely on these properties being appropriately expressed)

Question 2

What is the electrical property; conductivity?

Answer 2

It is the spread of electrical activity from cell to cell by their intercalated discs which contain nexus junctions (electrical spread) and mechanical coupling.

Question 3

What does excitability mean in terms of myocytes?

Answer 3

• Has a resting membrane potential

- Capable of repeatedly repolarising. (regenerative action potential)

Question 4

When creates the resting membrane potential?

Answer 4

• During diastole, K channels are open while other selective ion membrane channels are closed.
• K FLOWS OUT because of the transmembrane CONCENTRATION gradient created by Na/K ATPase
• However K also LEAKS back IN because of the ELECTRICAL gradient
• Equilibrium occurs at potential given by the nerst equation (Ek- expected to be -90mV)

(K out b/c chemical potential gradient = k in b/c electrical potential gradient)

Question 5

Are the resting membrane potential of myocytes normally -90mV?

Answer 5

No, the membranes are not completely impermeable to other ions such as Na and therefore these ions exert some force and the potential is pulled away from Ek(-90mV)

Question 6

What are the types of cells based on their action potentials?

Answer 6

Cells with rapid response

Cells with slow response

Question 7

Describe the depolarisation of AVN and SAN cells?

Answer 7

Cells of the AVN and SAN depolarise in phase 0 at a very slow rate 1-15 V s and this is associated with a very slow propagation of electrical activation.

Question 8

What properties do the SAN and AVN pacemaker membrane potentials have?

Answer 8

SA and AV node cells have unstable membrane potentials during the diastolic period “these creep towards threshold) aka diastolic depolarisation

Question 9

Describe the upstrokes of phase 0 in fast response cells;

Answer 9

Following external stimulus

• Upstroke (rapid depolarisation)
• Very rapid increase in Na permeability (fast iNa)
• Electrical and concentration gradients both inwards (membrane approaches nerst potential for Na)

Question 10

What are some examples of cells with rapid response?

Answer 10

Atria, ventricles, fast parts of the conduction system.

Question 11

What is the resting membrane potential and and threshold potential of rapid response cells?

Answer 11

Resting potential; -90mV

Threshold potential; -70mV

Question 12

Write some short notes on slow response cells;

Answer 12

Phase 0: Slow upstroke, Slow inward Ca [no fast Na current. (b/c above threshold)]

RMP; ~-55mV

Velocity propogation= is low

Question 13

Describe how pathology can change the excitability of myocytes;

Answer 13

Pathology i.e ischemia can change RMP i.e can change fast response cells to slow response and change the flow of events

Question 14

Describe the two gate model of Na channels and why they are not open above threshold potential

Answer 14

There is a change in configuration with different kinetics and voltage dependance.

• RMPl Activation gates are closed while inactivation gates are open.

At threshold potential (-70mV), there is a conformational change of the gates.

• Activation gates open allowing Na to flow in, allowing more activation gates to open.
• the voltage dependance of inactivation gates is opposite (voltage closes them) that of activation gates so there is 1-2 miliseconds before these close. This is the window for Na to enter the cell.
  i. e There are two voltage gates

Question 15

Describe phase one and two of fast response myocytes;

Answer 15

Phase One:
Early repolarisation
- Transient outwards (It0) K current and Cl

Phase Two:
Plateau phase
- Na channels inactivated (hence refractory)
- Inwards and outwards currents balanced
i) Slow inwards calcium current (ICa)
 - L type Ca channels
 - Release of Ca from SR
ii) Outward K current {iK1}
- Both currents decline across the plateau

Question 16

Describe the characteristics of iK1 channels.

Answer 16

• iK1 channels are open at RMP and are the major contributor to maintaining RMP.

K outwards

Question 17

Describe the characteristics of iK channels, when are they activated? How is their activity changed?

Answer 17

iK channels are activated near the end of phase 0 (slight repolarisation), but opening of the channels carrying this current is delayed until the end of phase 2 i.e phase 3

These channels are called the delayed rectifiers

• LOW ATP = INCREASE I.E ISCHEMIA (i.e IKatp)
• HIGH ACH = INCREASE I.E PARASYMP (I.e IKach)

Question 18

What generates the absolute refractory period?

Answer 18

Na channels display time-dependance and voltage dependance.

Their inactivation gates remained closed throughout phase 2 and half of three phase, this forms the ARP.

Once membrane potential drops below threshold potential, the inactivation gates and activation gates reset.

Question 19

What is the relative refractory period?

Answer 19

This is a time period in the second half of phase 3 and is created by the population of Na channel properties (i.e not all are uniform) and so all reset at different membrane potentials

Larger than normal stimulus to propagate AP

Question 20

Describe the refractoriness of perkinje fibres;

Answer 20

pirkinje fibres have long refractory periods and hence block many premature excitations of the atria which are conducted through the av junction.

This protection is epescially pronounced at slow heart rates because PF AP duration and hence refractory period varies inversely with heart rates.

Question 21

How is refractoriness different in the av node cells?

Answer 21

The av node’s refractory period does not change over the normal range of heart rates and actually increases at very rapid rates. Therefore when the atria are excited at hgih rates it is the av node which protect the ventricles from the high rate.

Question 22

What cells are found to have automacity?

Answer 22

Normally found in:

Slow response cells;

• SA node
• Some cells around the AVN

Fast response cells;
- His-pirkinje network.

Question 23

What creates automacity?

Answer 23

Decreased [IK] i.e less repolarised

Increased

• If (Na)
• I(Ca) (small contrib)

Question 24

Which outward currents are decreased in cells with automacity?

Answer 24

• Delayed rectifier iK

Question 25

What inward currents are increased in cells with automacity?

Answer 25

Inwards currents increased;

• iF (inward funny current), mainly inwards Na, activated at negative potentials
• iCa (slow inwards Ca channels), small contribution which continues into diastole. May contribute to early diastolic repolarisation.

Question 26

What mechanisms can alter the intrinsic rate of pacemaker discharge?

Answer 26

1) Alter the rate of depolarisation (slope)
2) Alter threshold potential
3) Alter maximum diastolic potential.

Question 27

How do catecholamines alter HR and how?

Answer 27

Catecholamines A & NA increase the magnitude of all the pacemaker currents, and also accelerate opening and closure of the iK channel. Overall effect is to increase the rate of diastolic depolarisation.

Question 28

How does AcH effect HR?

Answer 28

Main effect of Ach is to increase membrane K permeability (iK,Ach). Resulting in hyperpolarisation and slower rate diastolic depolarisation.

Question 29

Describe phase 3 and phase 4 of the fast type AP;

Answer 29

Phase 3 - Repolarisation
Outward K current

i) iK switched on after a delay (refer to earlier question)
ii) Reactivation of iK1 as membrane potential drops

Phase 4 - Resting
- iK1 high potassium conductance defines resting potential

Question 30

What are the background channels in myocytes active?

Answer 30

• CaATPase
• Na/Ca exchanger
• Na/K ATPase

Question 31

What is the interval-duration relationship?

Answer 31

• Duration of AP is determined partly by preceding diastolic interval.
• Rapid HR - Shorter AP

Question 32

Why is the SAN the dominant nodal tissue?

Answer 32

• Highest intrinsic rate
• If SAN fails, next pacemaker down takes over

Overdrive supression of other pacemakers

• Probably due to hyperpolarisation
• Keeps other cells from trying to take over

Question 33

What influences conduction velocities?

Answer 33

V is proportional to sqrt(r)

Dependant on depolarisation and amplitude of AP

Question 34

Roughly how long is the TRF?

Answer 34

~300ms

Question 35

What is automacity?

Answer 35

Ability of cells to initiate an electrical impulse through their own pacemaker activity or diastolic depolarisation

Question 36

What is maximum diastolic potential when talking about mechanisms of altering pacemaker discharge?

Answer 36

Maximum diastolic potential refers to the membrane potential achieved during diastole in cells that do not have a stable RMP

Question 37

What is diastolic depolarisation in cells with automacity?

Answer 37

It refers to when the ANS alters the rate of diastolic depolarisation i.e the slope during phase 4 of pacemaker cells. This is the rate of which the membrane depolarises before threshold is met in pacemaker cells