Cardiac Ion Channels & Action Potentials (complete) Flashcards

1
Q

Sketch a typical “fast” and “slow” cardiac action potential. Label voltage and time axes

A

GO DO IT! LOOK AT THE PICTURE

Fast = fast rising base

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2
Q

In which cells are fast cardiac APs found?

A

Muscular (myocardial) cells

  • In atrial muscles
  • In ventricular muscles
  • Cells of rapid conductive pathways
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3
Q

In which cells are slow cardiac APs found?

A

Pacemaker cells

  • SA node
  • AV node
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4
Q

What are the basics ion channels? Just to review

A
  • Channels “gate” closed/open
  • Direction of current flow depends on Vm and ion gradient (Nernst Potential, E(ion))
  • If Vm < E(ion), current into cell (depolarization)
  • If Vm > E(ion), current out of cell (hyperpolarization)
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5
Q

Describe the ionic mechanisms that are likely to account for the ability of pacemaker cells to generate rhythmic firing without neural input

A
  • Balance between I(Ca) and delayed rectifier current [I(Kr) and I(Ks)] => repolarization occurs shortly after AP peak
  • Then followed by slow depolarization => brings back to threshold
  • Induction of I(f) (hyperpolarization) allows cation fluxes
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6
Q

What’s the difference between inactivation and deactivation?

A
  • functionally different process
  • inactivation occurs if Vm is maintained —- tether ball closes the gate
  • deactivation occurs when Vm changes and activation gate just closes w/o use of inactivation gate
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7
Q

Describe the significance of the I(K1) channels in myocardial cells that have “fast” APs

A
  • Inward rectifier potassium currents
  • lets current in but cell never goes below E(k)
  • Holds the cells near E(k) b/c not much K+ current is let out
  • Think Phase 4
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8
Q

Describe the significance of the I(f)/I(h) channels in myocardial cells that have “slow” APs

A
  • These are time-dependent cation current dependent
  • Triggered by hyperpolarization
  • Drives voltage towards the reversal potential => may play role in pacemaker potential
  • These currents are the reason why you see a slight incline in the slope of phase 4 before the AP
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9
Q

Describe the mechanism and significance of overdrive suppression

A
  • AV node propagation driven by APs originating in SA node and extend to ventricles
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10
Q

Define absolute refractory period

A
  • Period of time following fast cardiac APs
  • Second AP cannot be initiated until most of the inactivation of I(Na) is removed
  • This period is during the depolarization and repolarization phase
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11
Q

Define relative refractory period

A
  • Refers to the hyperpolarization phase

- Over when normal threshold is reached

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12
Q

HR is controlled by which cells? Where?

A
  • Pacemaker cells in the sinoatrial node (SA node)
  • Rate modulated by ANS
  • Fire intrinsically at ~100/min
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13
Q

Where are other cells besides those around the SA node that are capable of spontaneous activity?

A

Atrioventricular (AV) node

  • Takes over initiation of HR if there’s something wrong with the SA node
  • called ectopic pacemakers
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14
Q

What is HERG?

A
  • An anti-target tested in preclinical eval of new drugs
  • HERG produces I(Kr)
  • Important for duration of slow and fast APs
  • Reducing I(Kr) can result in arrhythmias
  • HERG blocked by diverse compounds
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15
Q

Describe sodium ion channels or I(Na). During which phase do these channels open?

A
  • similar to neurons/skeletal muscle
  • Depolarization causes them to activate rapidly => then inactivate
  • open during phase 0
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16
Q

Describe calcium channels with L-type current

A
  • High voltage activated
  • Both voltage- and calcium- dependent inactivation
  • Found in ventricular/atrial myocardium, SA and AV nodes, and conductive pathways
17
Q

Describe calcium channels with T-type current

A
  • Low voltage activated
  • voltage dependent inactivation
  • Found in SA node and nervous system
18
Q

What are two groups of time-dependent potassium channels?

A

1) I(Kto)

2) I(Kr) and I(Ks)

19
Q

Describe I(Kto)

A

Depolarization causes both activation and inactivation on a time scale slightly slower than the sodium channel

20
Q

Describe I(Kr) and I(Ks)

A

I(Kr): rapid delayed rectifier

I(Ks): slow delayed rectifier

Depolarization causes activation of these two currents in 20-100 ms

21
Q

Describe I(K1)

A
  • Inward rectifier channel (not gated)
  • Steeply voltage dependent
  • Readily conduct inward K+ current at potential below E(k)
  • hold cells near E(k) between APs
22
Q

Describe I(Kach)

A
  • GIRK tetramer
  • Current is increased in response to ACh acting on muscarinic receptors
  • Important in ability of PNS to slow pacemaker activity in SA node
23
Q

Describe I(f)

A
  • Funny current!
  • Turned out by depolarized potentials
  • Turned on at hyperpolarized potentials
  • Permeable to Na+ and K+
  • Thought to be activated at both depolarized and hyperpolarized potentials => however current flow depends on hyperpolarization b/c inactivated at depolarized potentials
  • Thought to play important role in pacemaking by SA nodal cells