L11 Electrical activity of the Heart

Question 1

What drives ion to move across membrane?

Answer 1

Different concentration of an ion on either side of a membrane:
Concentration gradient

Question 2

What opposes further ion movement?

Answer 2

movement charge sets up electrical gradient

Question 3

When does net movement stop?

Answer 3

Net movement ceases when electrical and chemical gradients are exactly balanced

At equilibrium potential for the ion

Question 4

equilibrium potential for the ion can be calculated by?

Answer 4

Nernst equation: e.g. K
Ek = (RT/F) ln ([K0+]/[Ki+])

 EK = potassium equilibrium potential (= -90mV in heart)
 R = gas constant
 T = temperature (constant in body)
 F = Faraday constant
(RT/F= constant (in general))

Question 5

Ions have same or diff equ potential?

Answer 5

different equilibrium potential

Question 6

What is membrane potential? Vm

Answer 6

electrical gradient across the cell membrane (can change over time  action potential)

Question 7

What does Vm depend on?

Answer 7

Depends on both:

1. Concentrations of ions on either side of the membrane; and
2. Permeability of the membrane to each ion

Question 8

What is ture if Vm is close to one ion’s equilibrium potential?

Answer 8

If much more permeable to one ion: that ion can easily cross the membrane to approach equilibrium potential)

Question 9

If membrane is equally permeable to two ions, what would Vm be?

Answer 9

If equally permeable to two or more ions: VM close to average of the equilibrium potentials for those ions

Question 10

How can rapid changes to Vm be induced?

Answer 10

Changing permeability of membrane to one or more ions (e.g. opening / closing of channels)

Takes very long to change concentration of ions

Question 11

Which cells show fast response AP? Which ones slow?

Answer 11

Fast:
Atrial muscle
Ventricular muscle
Purkinje fibres

Slow:
Sinoatrial (SA) node
Atrioventricular (AV) node

Question 12

Fast or Slow response AP cells show pacemaker activity?

Answer 12

Slow

Question 13

Fast or slow response AP cells include rapid depolarization response

Answer 13

Fast

Question 14

What is fast response AP initiated by? What is it depolarized by?

Answer 14

Initiated by electrical signal from adjacent cell

Voltage-gated (fast) Na+
channels opening  (PNa increase)

Question 15

When Voltage-gated (fast) Na+ channels open in fast AP cell membrane, what closes?

Answer 15

Inward-rectifier K+ channels close

Question 16

When fast response AP cell is at rest, what maintains resting potential? At rest cell is impermeable to which 2 ions?

Answer 16

Inward-rectifier K+ channels open.
= highly permeable to K+ so resting Vm is close to EK (stable at ~-90 mV)

Highly impermeable to Na+ and Ca2+

Question 17

At what Vm does V-gated Na+ channels open? What is the consequence of the opening?

Answer 17

When VM reaches -70 mV threshold

Rapid depolarization:
Membrane most permeable to Na+ >Vm approaches ENa

Question 18

Fast AP.
What is Partial repolarisation?
Which 2 channels are involved?

Answer 18

Voltage-gated (fast) Na+
channels remain open only for a very short time and quickly close
decreased permeability to Na+ >Vm moves away from ENa

Transient outward K+ channels also open very briefly > help to partially
repolarise the membrane

Question 19

What phase follows partial repolarisation in fast AP cells?

Answer 19

plateau (“slow inward current”

Question 20

What is plateau (“slow

inward current”) dependent on?

Answer 20

L-type Ca2+ channels

Question 21

What triggers opening of L-type Ca2+ channels in fast AP cells?

Answer 21

Depolarisation to -40 mV triggers opening of voltage-gated Ca2+ channels (L-type:
long duration: slow to open and close)
VM remains close to ECa

Question 22

What starts repolarisation after plateau?

Answer 22

1. Voltage-gated L-type Ca2+ channels close

2. Several K+ channels open:

Question 23

Which K+ channels open during rapid repolarisation phase in fast response AP cells?

Answer 23

 1st : slowly-activated delayed rectifier K+ channels

 Then: rapidly-activated delayed rectifier K+channels

 Finally: inward rectifiers re-open (voltage-activated: when Vm is negative enough)

Question 24

During rapid repolarisation in fast AP cells, what is the cell most permeable to?

Answer 24

Cell most permeable to K+

so Vm moves towards EK

Question 25

In slow response AP cells, is there rapid depolarization?

Answer 25

No voltage-gated fast Na+ | channels, so no

Question 26

What is slow response AP DEPOLARIZATION started by? (remember slow tcells have pacemaker potential)

Answer 26

Initiation (spontaneous): repolarization (from previous AP repolarisation ) to -40 mV triggers opening of “funny channels” Na channels (gNa: permeable to Na+ so PNa increases)

Question 27

What happens in slow AP cells when funny channels are opened and PNa increases?

Answer 27

Funny channels open and PNa increases, whilst K channels close so Vm moves further away from EK Cell is further depolarized

Question 28

When Vm in slow AP cells finally reach threshold of -40mV, what happens?

Answer 28

When VM reaches threshold (-40 mV), voltage-gated L-type slow Ca2+ channels open Cell becomes most permeable to Ca2+ so Vm moves close to ECa > AP

Question 29

Is there partial repolarisation and plateau in slow AP cells?

Answer 29

NO

Question 30

When is gCa the highest in slow AP cells?

Answer 30

Peak of Vm

Question 31

When is gNa the highest?

Answer 31

Small peak at the end of previous AP after complete repolarisation (funny channels are Na+ channels)

Question 32

When is gK the highest and lowst in slow AP cells?

Answer 32

gK highest just before the end of complete repolarisation of previous AP lowest at 40mV threshold just before depolarisation to AP

Question 33

Which channel causes rapid repolarisation in slow AP cells?

Answer 33

Voltage-gated L-type slow Ca2+ channels close SPONTANEOUSLY (opening = time-dependent) Decrease in PCa cause Vm to move away from ECa

Question 34

When slow AP cell is depolarized and PCa increases, what other channel also opens and increase said ions permeability?

Answer 34

K+ channels open (triggered by depolarization) and increase PK:  1st: IKs:slowly-activated delayed rectifier K+channels  Then: IKr:rapidly-activated delayed rectifier K+channels  Finally: IK1:inward rectifiers re-open

Question 35

Slope of which potential controls HR?

Answer 35

Slope of pacemaker potential controls heart rate (how long it takes to reach threshold to open gCa): Steeper slope= faster heart rate

Question 36

What is the intrinsic rate of pacemaker activity in SA node?

Answer 36

``` fastest intrinsic rate of pacemaker activity (~ 100 beats/min) ```

Question 37

How can electrical activity spread between cardiac cells? Where?

Answer 37

gap junctions = specialised areas of low electrical resistance In longitudinal region of the extensive membrane folds where 2 cells parallel each other

Question 38

Where are muscle fibres (actin filaments) strongly joined? name, where in muscle

Answer 38

Intercalated disks Always occur at Z-line Attached to sacromere

Question 39

Gap junctions are what?

Answer 39

Connexons = hemi-channels (6 subunits) on adjacent cells connexons on each cell membrane dock > connexin 43 channel

Question 40

What happens when Connexin 43 channels are depolarized? What is the domino effect?

Answer 40

V-gated Ions flow from 1st depolarised cell to 2nd cell...etc Lowers VM of 2nd cell to threshold level (depolarized) Trigger action potential in 2nd cell whole heart chamber can depolarize and contract at the same time

Question 41

Apart from the gap junctions, what other conducting pathways are there? (3) What are these for?

Answer 41

1. Anterior intermodal band 2. Middle intermodal band 3. Posterior intermodal band For depolarization to spread to furthest part of atria so both atria contract almost simultaneously

Question 42

AV node conduction is slow. Why?

Answer 42

Atria finish contracting before ventricular contraction starts

Question 43

Purkinje fibre network | How is it arranged?

Answer 43

 Arranged in right and left branches of Bundle of His  Runs down interventricular septum  Branches extensively throughout ventricles

Question 44

Why is Purkinje fibre network necessary?

Answer 44

Action potential spread quickly to all parts of ventricles

Question 45

Rank the conduction speeds of nodes and fibres in ascending order (slowest first)

Answer 45

slowest= AV node (0.05m/s) > Atrial and ventricular muscle (0.5m/s) > Bundle of His (1m/s) > Purkinje network (5m/s)

Question 46

How long does cardiac muscle AP last? How does this cycle divide?

Answer 46

Cardiac muscle action potential lasts ~250 msec: First ~ 200 msec = absolute refractory period: Remaining 50 msec = relative refractory period

Question 47

What is refractoriness due to?

Answer 47

due to gates on Na+ | channels

Question 48

Explain how Na+ channels cause refractoriness.

Answer 48

At rest: Fast gates closed, slow gates open, channel cannot conduct Depolarization: Fast gates open fast, slow gate close slow For a limited time, both gates are open and Na+ passes through

Question 49

Relate absolute refractory period to fast and slow Na+ gates.

Answer 49

First ~ 200 msec = absolute refractory period: Slow gates are closed > cell is completely inexcitable when Vm is negative enough > Impossible for another stimulus to produce another AP

Question 50

Relate relative refractory period to fast and slow Na+ gates.

Answer 50

Remaining 50 msec = relative refractory period When Vm becomes sufficiently negative again (-50mV):  Fast gates quickly close  Slow gates slowly open ** Slow gate partly open = relative refractory period

Question 51

What happens if AP occurs during relative refractory period?

Answer 51

If AP occurs: slow gates close more quickly (because only partly opened) Stronger stimulus can produce a smaller, shorter AP

Question 52

What is contractile response due to? (which ion)

Answer 52

Ca2+ movement which takes time

Question 53

What is contractile response latency?

Answer 53

10 msec

Question 54

How long is total contractile response and when does it peak?

Answer 54

300msec total | Peaks before 200 msec (within absolute refractory period)

Question 55

Why is there no tetanus occurring in relation to AP and contractile response?

Answer 55

AP lasts as long as contractile response (some rapid filling of ventricle has already taken place) only minimal summation of contractile responses no tetanus can occur

Question 56

Why is cardiac muscle unlike skeletal muscle in its contraction?

Answer 56

Cardiac muscle must always relax between contraction (unlike skeletal muscle) so only minimal summation and no tetanus can happen