Cardiac Ion Channels & Action Potentials (complete) Flashcards Preview

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


Fast = fast rising base


In which cells are fast cardiac APs found?

Muscular (myocardial) cells

- In atrial muscles
- In ventricular muscles
- Cells of rapid conductive pathways


In which cells are slow cardiac APs found?

Pacemaker cells

- SA node
- AV node


What are the basics ion channels? Just to review

- 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)


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

- 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


What's the difference between inactivation and deactivation?

- 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


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

- 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


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

- 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


Describe the mechanism and significance of overdrive suppression

- AV node propagation driven by APs originating in SA node and extend to ventricles


Define absolute refractory period

- 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


Define relative refractory period

- Refers to the hyperpolarization phase
- Over when normal threshold is reached


HR is controlled by which cells? Where?

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


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

Atrioventricular (AV) node

- Takes over initiation of HR if there's something wrong with the SA node
- called ectopic pacemakers


What is HERG?

- 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


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

- similar to neurons/skeletal muscle
- Depolarization causes them to activate rapidly => then inactivate
- open during phase 0


Describe calcium channels with L-type current

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


Describe calcium channels with T-type current

- Low voltage activated
- voltage dependent inactivation
- Found in SA node and nervous system


What are two groups of time-dependent potassium channels?

1) I(Kto)
2) I(Kr) and I(Ks)


Describe I(Kto)

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


Describe I(Kr) and I(Ks)

I(Kr): rapid delayed rectifier

I(Ks): slow delayed rectifier

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


Describe I(K1)

- 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


Describe I(Kach)

- 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


Describe I(f)

- 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