Cardiac Ion Channels & Action Potentials (complete) Flashcards
Sketch a typical “fast” and “slow” cardiac action potential. Label voltage and time axes
GO DO IT! LOOK AT THE PICTURE
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