107- Normal Cardiac Electrical Activity Flashcards

1
Q

List the 3 factors that contribute to the plateau of the cardiac action potential

A
  1. The cell is permeable to Ca2+ due to ICa (L-type channel)
  2. IK1 is blocked; K+ cannot get out
  3. IK is slow; it only begins to contribute to K+ outflow near the end of the plateau (phase 3)
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2
Q

In the SA Node, which current is responsible for phase 3?

A

K+ channels open

K+ flows out of the cell, hyperpolarizing it. L-type Ca2+ channels close

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3
Q

Which ions have a negative equilibrium potential?

A

K+ and Cl-

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4
Q

Describe the steps that occur in repolarization (phase 3)

A

In general: ICa-L gradually inactivates, and IK activates

  • The f gate closes, halting inward Ca2+ flow (inactivation)
  • Vm becomes more negative
  • Inward rectification by IK1 is decreased (less K+ in)
  • K+ outflow increases via IK1 (no longer blocked)
  • IK becomes more active as Vm becomes more negative
    • IKs = slow
    • IKr = rapid
    • IKur = ultrarapid
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5
Q

Which ion is responsible for the “slow response only” cardiac action potential?

Describe some of the characteristics of this kind of action potential

A

Ca2+ (when INa is inhibited/inactivated)

Compared with an INa phase 0 upstroke, a Ca2+ driven upstroke will have…

  • Slower time dependency of activation and inactivation
  • Slower upstroke velocity
  • Slower conduction velocity between cells
  • Lower safety margin - this decreases the probability of successful propagation between cells
  • Longer refractory period = longer action potential duration
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6
Q

Which ions have a positive equilibrium potential?

A

Na+, Ca2+

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7
Q

What is the mechanism of fast response action potentials vs slow response?

Under what conditions does each type of action potential occur?

A

Fast response APs are governed by INa. These occur under normal contitions in most cells

Slow response APs are governed by ICa-L. These occur if the resting membrane potential is not negative enough to activate INa, such as in pacemaker cells

For example, at a resting membrane potential of -60 mV, the m gate for the Na+ channel is open, but the h gate is inactivated. At this voltage, the d and f gates for Ca2+ may open, but they are slower. The result is a longer, less powerful action potential.

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8
Q

What is the equation to calculate resting membrane potential using conductance?

A

Note: if other ions have significant conductance for a particular cell, add them as well

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9
Q

Which current drives phase 0 in cardiomyocytes?

A
  • INa into the cell through rapid Na+ channels
    • Controlled by m (activation) and h (inactivation) gates
  • Supported by ICa into the cell through slow L-type Ca2+ channels (but these are slower and more active in phase 2)
    • Controlled by d (activation) and f (inactivation) gates
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10
Q

What are the 3 types of dependencies that a membrane channel may have?

A

Voltage dependence

Time dependence

Ligand dependence

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11
Q

Which cells in the body exibit the following action potential?

A

Cells with pacemaker activity

  • SA Node (Primary pacemaker)
  • AV Node
  • Bundle Branches and Purkinje Fibers
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12
Q

Under what conditions would Ca2+ be responsible for the phase 0 upstroke?

A

If INa is inhibited

(potentially due to leaky K+ channels resulting in less negative Vm)

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13
Q

Which current is responsible for phase 1?

A

Ito

Transient outward K+ current

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14
Q

In a typical cell at baseline, which ions typically have the highest conductance?

A

Na+, K+

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15
Q

In the SA node, which mechanisms are responsible for phase 4?

A
  1. If, or “Funny current” that carries Na+. Sodium leaks into the cell, depolarizing it to the threshold potential.
  2. K+ channels are closed/less active
  3. Na+/Ca2+ exchanger is activated due to the release of Ca2+ from the sarcoplsamic reticulum, via RyRs.
    1 Ca2+ out for 3 Na+ in = Net inward Na+ current
  4. As the pacemaker cell gets closer to the threshold potential, t-type Ca2+ channels open. Ca2+ rushes in, and threshold is reached
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16
Q

Which current is the main driver of resting membrane potential (phase 4)?

A

IK1 - The inward rectifying current

Note: IK1 is not active in the plateau phase (phase 2). Flow of K+ out of the cell through the inward rectifying channel is blocked (maybe by Mg2+); K+ cannot flow out via IK1 to repolarize the cell

17
Q

What is the equilibrium potential of Na+ in a typical cardiac myocyte?

A

~70 mV

18
Q

Which K+ currents contribute to both repolarization in phase 3 and resting membrane potential in phase 4?

A

IK - a combination of K+ currents

  • IKs = slow
  • IKr = rapid
  • IKur = ultrarapid
19
Q

What is the equilibrium potential of Ca2+ in a typical cardiac myocyte?

A

132 mV

20
Q

Which ions have a higher concentration outside of the cell than in?

A

Na+, Cl-, Ca2+

21
Q

What is the Nernst equation for a cation?

A

(Note: [ion]out is in the denominator and [ion]in is in the numerator for anions)

22
Q

What is conductance (g) of an ion?

A

Conductance is the relative contribution of any ion species at a given time point

It is basically the opposite of resistance

23
Q

What is the equilibrium potential of K+ in a typical cardiac myocyte?

A

-88 mV

24
Q

Which current drives phase 2?

A

ICa flows in (and K+ does not flow out)

The L-type Ca2+ channels remain open, allowing Ca2+ to flow into the cell. This keeps the Vm of the cardiomyocyte positive

K+ does not flow out to repolarize the cell because…

  • IK1, the inward rectifier current, is closed
    • Inward rectifier = ions flow in more easily than out
    • Mg2+ sits on the intracellular side, blocking K+ outflow
  • IK, through the rectifier channel is slow to activate; it does not play a role until phase 3
25
Q

Control of INa during the upstroke of the cardiac action potential:

The cell is at rest at -85 mV. The m gate is closed, and the h gate is open

What voltage triggers the opening of the m gate?

What voltage triggers the closing of the h gate?

A

Opening of the m gate and closing of the h gate are both triggered when the myocyte reaches its threshold potential

However, the m and h gates operate on different time dependencies

The m gate is faster and swings open, allowing Na+ to flow into the cell before the h gate has a chance to close

26
Q

Which current drives phase 3?

A

IK is active (and ICa-L gradually inactivates)

27
Q

INa is controlled by m (activation) and h (inactivation gates)

Describe the state of the m and h gates at each phase of the cardiac action potential

A
28
Q

What current is responsible for phase 0?

A

Increased Ca2+ conductance through L-type Ca2+ channels

29
Q

How is phase 4 in the pacemaker cells (shown) different from phase 4 in ventricular myocytes?

A

In pacemaker cells, the membrane is slowly depolarizing in phase 4 due to If, or “funny current” that allows Na+ to leak into the cell, T-type Ca2+ channels, and Na+/Ca2+ exchanger activity.

In ventricular myocytes (and all other non-pacemaker cells), phase 4 is flat becuase there is no current that depolarizes the cell automatically. Changes to membrane potential occur only in response to stimuli (such as nearby action potentials).

30
Q

Which ions have a higher concentration inside of the cell than out?

A

K+ only