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CVDM > Cardiac Action Potential and Excitation-Contraction Coupling > Flashcards

Cardiac Action Potential and Excitation-Contraction Coupling Flashcards

1
Q

What law is biolectricity based on?

A

Ohm’s law - Current = Voltage/Restistance (I=V/R)

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2
Q

What is voltage?

A

Electrical driving force for current (ions) to flow

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3
Q

In bioelectricity, where does voltage come from?

A

Membrane potential

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4
Q

Membrane potential:
1. What is it?
2. What does it arise as a result of?
3. What does it determine?

A
  1. It is the electrical driving force for ionic fluxes
  2. Arises as a result of separation of charge across a biological barrier
  3. Determines the size and direction of current flow through ion channels alongside the chemical gradient
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5
Q

What is meant by voltage clamp and a current clamp?

A

Voltage clamp - if you fix the voltage you can get the current
Current clamp - if you fix the current you can get the voltage

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6
Q

Resting ionic distributions across sarcolemma:
Sodium is high/low on the outside and high/low on the inside

A

Sodium is high on the outside and low on the inside

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7
Q

Resting ionic distributions across sarcolemma:
Potassium is high/low on the outside and high/low on the inside

A

Potassium is low on the outside and high on the inside

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8
Q

Resting ionic distributions across the sarcolemma:
Calcium is high/low/very low on the outside and high/low/very low on the inside

A

Calcium is low on the outside and very low on the inside

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9
Q

Resting ionic distributions across sarcolemma:
Chloride is high/low on the outside and high/low on the inside

A

Chloride is high on the outside and low on the inside

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10
Q

Give the values for the resting ionic distributions across the sarcolemma on the outside and inside:
Na+
K+
Ca2+

A

Na+ - outside = 140, inside = 15
K+ - outside = 5, inside = 140
Ca2+ - outside = 2, inside = <0.001

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11
Q

What does the Nernst equation calculate?

A

The membrane potential in which forces driving ion movement are in equilibrium (no net movement of ions)

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12
Q

What determines the equilibrium potential of ions?

A

The Nernst equation

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13
Q

What is the equilibrium potential of sodium ions?

A

+59mV

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14
Q

What is the equilibrium potential of potassium ions?

A

-89mV

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15
Q

What is the equilibrium potential for calcium ions?

A

+140mV

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16
Q

What is the equilibrium potential for chloride ions?

A

-59mV

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17
Q

What is patch clamp electrophysiology used to measure?

A

Bioelectricity

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18
Q

Describe the technique of patch-clamp electrophysiology

A
  1. Polished pipette filled with a mock intracellular solution is lowered onto the cell
  2. Suction is applied to achieve a tight electrical and physical seal between the glass and cell membrane
  3. The voltage/current of this piece of membrane is now under your control
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19
Q

Describe the structure of a voltage-gated Na+ channel

A

4 homologous domains (D1-D4) with each domain containing 6 segments (S1-S6)

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20
Q

What segment is a “voltage-sensor”

A

S4 transmembrane segment

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21
Q

Describe the cycle of the voltage-gated Na+ channel

A
  1. At rest it is closed
  2. It is activated by applying a depolarising pulse, the channel opens and sodium goes into the cell
  3. It enters an inactivated state almost immediately after opening
  4. It enters intermediate inactivated state before going back to resting state
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22
Q

What shape will the current voltage relationship be if you plot it?

A

U-shaped

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23
Q

What is the functional unit of the Na+/K+ ATPase?

A

𝛂𝛃 subunit

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24
Q

How many domains are on an alpha subunit of the Na+/K+ ATpase?

A

10

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25
Q

What binds to the alpha subunit of the Na+/K+ ATPase?

A

Na+, K+ and ATP

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26
Q

How many domains are on the beta subunit of the Na+/K+ ATPase?

A

1 - single transmembrane domain

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27
Q

What is the function of the beta subunit of the Na+/K+ ATPase?

A

Trafficking of the complex to the sarcolemma - ensures that Na+/K+ ATPase ends up in the sarcolemma

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28
Q

What is the gamma subunit of the Na+/K+ ATPase also known as?

A

Phospholemman

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29
Q

What is the function of phospholemman?

A

Acts as on/off switch for Na+/K+ ATPase

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30
Q

What happens to the gamma subunit of Na+/K+ ATPase when phosphorylated/de-phosphorylated?

A

Phosphorylated - unbound
De-phosphorylated - binds and switches off function of Na+/K+ ATPase

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31
Q

The gamma subunit of Na+/K+ ATPase is unbound when phosphorylated/de-phosphorylated

A

Phosphorylated

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32
Q

What happens when the gamma subunit of the Na+/K+ ATPase is dephosphorylated?

A

It binds and switches off the function of Na+/K+ ATPase

33
Q

In the Na+/K+ ATPase electrogenic pump, sodium ions move in to/out of the cell and potassium ions move in to/out of the cell?

A

Sodium ions move out of the cell and potassium ions move in to the cell

34
Q

How many sodium ions move out of the cell and how many potassium ions move in to the cell via Na+/K+ ATPase

A

3 sodium ions out of the cell for every 2 potassium ions in to the cell

35
Q

Where does the energy for each cycle of Na+/K+ ATPase pump come from?

A

Hydrolysis of ATP

36
Q

What 2 things are responsible for setting the resting membrane potential?

A

Relative permeability and concentrations of Na+ and K+

37
Q

What is the relative permeability of Na+:K+?

A

1:100
At rest, potassium ions are 100x more permeable to across the membrane than sodium ions

38
Q

In the heart, what determines the resting membrane potential and why?

A

K+ movements because they are moving at rest

39
Q

What are the 4 types of K+ channels?

A

Voltage-gated
Inwardly rectifying
Hyperpolarisation activated
Ca2+ activated

40
Q

What is the main K+ channel responsible for maintaining resting membrane potential in non-modal cardiomyoctes?

A

Inwardly rectifying K+ channels

41
Q

True or false:
In voltage-gated K+ channels, the current activity changes with voltage?

A

True

42
Q

Describe the activity of voltage-gated K+ channels at resting membrane potential

A

They have no activity

43
Q

How do inwardly rectifying K+ channels work?

A

Magnesium blocks pore and as the membrane depolarises the blockage is relieved

44
Q

According to the Nernst equation, what is the equilibrium potential for Na+?

A

+70mV

45
Q

According to the Nernst equation, what is the equilibrium potential for K+?

A

-88mV

46
Q

Why is the membrane permeability for K+ higher than Na+?

A

Na+ channels are mostly closed at rest

47
Q

What are the 5 phases of cardiac action potential?

A

Phase 0 - depolarisation
Phase 1 - early repolarisation
Phase 2 - plateau phase
Phase 3 - late depolarisation
Phase 4 - Stabilisation of the resting membrane potential

48
Q

What happens in phase 0 of the cardiac action potential?

A

The opening of sodium channels causes depolarisation
Membrane potential goes from -80/-90mV to +40/+50mV

49
Q

What protein underlies the depolarisation phase of the cardiac action potential?

A

NaV1.5

50
Q

What is phase 1 of the cardiac action potential mediated by?

A

Transient outward K+ channels

51
Q

What are the 2 components of the transient outward K+ currents of phase 1 of the cardiac action potential?

A

Fast (Kv4.2 and Kv4.3) and slow (Kv1.4)

52
Q

True or false - there is a second transient outward current in phase 1 of the cardiac action potential?

A

True - carried by a Ca2+ activated Cl- current

53
Q

What happens in phase 2 of the cardiac action potential?

A

There is a mixture of inward and outward currents.
The sum activity means membrane potential doesn’t really change resulting in plateau

54
Q

What happens in phase 3 of the cardiac action potential?

A

There is Ca2+ dependent inactivation of L-type calcium channels which starts to bring the membrane potential back down

55
Q

How does an action potential trigger a contraction?

A

It triggers a rise in cytoplasmic Ca2+ concentration

56
Q

Stages of cardiac excitation and contraction coupling

A
  1. T-tubule depolarisation opens LTCC
  2. Ca2+ entry via LTCC raises conc. Ca2+ in junctional cleft
  3. Calcium activates clusters of RyR2 in junctional sarcoplasmic reticulum
  4. Ca2+ binds to myofilaments and initiates contractions
  5. Intracellular Ca2+ is removed
  6. Reduction of conc. Ca2+ causes unbinding of Ca2+ from myofilaments leading to relaxation
57
Q

In what form are calcium ions released from the sarcoplasmic reticulum?

A

Released as sparks

58
Q

True or false:
Calcium sparks only occur spontaneously

A

False - they can occur spontaneously or be evoked by depolarisation of cell patches

59
Q

What are the 3 means by which Ca2+ can be removed from the cytoplasm to allow relaxation?

A

By SERCA (sarcoendoplasmic reticulum Ca2+ ATPase) back to SR
By NCX (sodium calcium exchanger) out of cardiomyocyte
By PMCA (plasmalemmal Ca2+ ATPase) out of cardiomyocyte

60
Q

What isoform of SERCA is usually found in the cardiomyocyte?

A

SERCA2a

61
Q

How does SERCA work to remove Ca2+ back into the sarcoplasmic reticulum?

A

Moves Ca2+ against the concentration gradient through hydrolysis of ATP

62
Q

What does phospholamban (PLB) do?

A

Endogenous inhibitor which regulates the removal of Ca2+ via SERCA

63
Q

How does NCX work to remove Ca2+ out of the cardiomyocyte?

A

Uses the sodium gradient (high on outside, low on inside) to move Ca2+ out of cell against concentration gradient

64
Q

In the normal mode of the NCX, how many sodium ions are moved in to the cell for how many calcium ions moved out?

A

3 Na+ in for 1 Ca2+ out
3 positive ions in for 2 positive ions out resulting in depolarisation (the reverse is hyperpolarising)

65
Q

How is Ca2+ balance in the SR maintained?

A

Ca2+ entry via LTCC and exit via NCX

66
Q

What is the difference in cardiomyocyte movement when there is normal Ca2+ maintenance vs overload in the SR?

A

Normal Ca2+ maintenance = whole cell contraction
Overload = cardiomyocyte quivers rather than contracts

67
Q

What is the issue caused by the cardiomyocyte quivering rather than contracting when the SR is overloaded with Ca2+?

A

Can lead to delayed after-depolarisations and lead to re-enrant arrhythmias

68
Q

Where to neurogenic hearts receive their pacemaker commands from?

A

Neuronal innervation from an extracardiac source: the cardiac ganglion

69
Q

Where do myogenic hearts receiver their pacemaker commands from?

A

They have their own intrinsic muscle-derived pacemaker

70
Q

What is the difference between the contraction in neurogenic hearts vs myogenic hearts?

A

Neurogenic hearts - all parts of the heart tend to contract simultaneously
Myogenic hearts - tend to contract sequentially - wave of contraction spreads monotonically from one end to the other

71
Q

Is the mammalian heart neurogenic or myogenic?

A

Myogenic - although is a functional mixture between a neurogenic and myogenic heart

72
Q

True or false:
The action potential shape of the cardiomyocytes of atrial ventricular muscle is the same as the nodal action potential shape

A

False

73
Q

True or false:
The pacemaker action potential is more positive than the resting membrane potential

A

True - -50mV compared to -90mV

74
Q

Why is upstroke a lot slower in the action potential of nodal cells?

A

There are no voltage gated sodium channels

75
Q

What are the phase of the action potential in nodal cells?

A

Phase 0
Phase 3
Phase 4

76
Q

There are decreased/increased potassium channels in phase 3 of the action potential in nodal cells compared to the action potential of other cardiomyocytes

A

There are increased potassium channels

77
Q

What is phase 4 of the action potential in nodal cells?

A

The pacemaker potential

78
Q

What is the ‘funny current’?

A

A hyperpolarisation activated current which is carried by Na+ K+ and is involved in phase 4 of the action potential of nodal cells

CVDM (16 decks)

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