Memorizing is not important, but understanding the mechanism is:
Partial inactivation of Na+ channels
- Hypoxia causes extracellular K+ to rise, depolarizing the cells, resulting in rise in resting membrane potential.
- Potential mechanism includes inhibition of ATP dependant Na/K pump.
- At more negative RMP, more Na channels are available for depolarizing current. With a more positive RMP, more Na channels are in inactivated unavailable state, thereby decreasing conduction velocity during phase 0.
- Ventricular level
– Normal conduction pattern – an impulse is conducted down two branches of a Purkinje fiber twig into the ventricular wall. These impulses collide and extinguish each other after exciting the muscle cells to contract.
– Ischemia slows down the conduction in the damaged pathway. Meanwhile, conduction down an undamaged pathway results in excitation of a large number of undamaged cells in the ventricular wall (constituting a large electrical stimulus) on the opposite side of the damaged region. This large electrical stimulus is strong enough to slowly conduct through the damaged region, summate, and elicit an action potential in the depressed region that conducts upward in a retrograde direction.
– As long as the impulse does not run into cells within their effective refractory period, the reentrant circuit can function as an ectopic ventricular pacemaker. If rapid enough the circuit can produce a sustained ventricular tachycardia.
- AV node reentry: most of us know this:
- AV block
– Recall that vagal stimulation increases the strength of repolarizing (K) currents, and reduces the strength of the L-type Ca current in this region (phase 4 and 0). The net effect of vagal stimulation will be to increase the PR interval, and increase the ERP in the AV node.
- Early AD
– In hypokalemia, drugs induced; classic example is Tdp
– Ikr conductance is decreased, which reduces the efflux of K+ during the plateau, leading to prolongation of APD.
– If net inward currents during phase 3 become larger than outward currents, this can form an EAD (as cells are more depolarized than repolarized).
- Delayed AD
– Early AD results from conductance problem in the potassium current, but DAD (during phase 3) results from the rise of intracellular calcium due to digoxin or catecholamines.
– Eg digoxin leads to accumulation of intracellular Ca++, this causes a reversal of Na/CA exchanger (normally Ca is pumped inside and Na outside, now Na is pumpd inside and Ca outside, possibly as a protective mechanism)
– Na influx causes depolarization of the cells during repolarization period (phase 3), leading to DAD
** It does not affect phase 2, because (in my understanding) the balance between potassium efflux and calcium influx is still maintained in phase 2.
Dispersion of repolarization
- In later stage of phase 3, cellular depolarization happens (current from sodium or calcium channels) but the membrane potential still remains negative as it is “overpowered” by the amount of K+ efflux.
- M cells have longer APD than epicardial cells and endocardial cells. In normal condition, the spread of current is minimal and does not induce any after-depolarization.
- Under the combination of such drugs and slowing of the heart rate, the M cell APD widens disproportionately, resulting in an abnormally large dispersion of APD values between regions (as indicated by the width between the two vertical lines). A dispersion of repolarization can induce a spread of current from the depolarized M cell region to the epicardial region that has regained its excitability.
- When the M-cells have finished repolarizing (phase 4), the current gradient between epicardial and M cells lead to spread of the current to M-cells which in turn also spreads the current to endocardial cells.
- Net effect is after-depolarizations in all three layers of ventricular cells. The classical example is long QT induced Tdp.