Afterdepolarization

A cell generates late afterdepolarizations (typically induced by catecholamines or digitalis) following a complete repolarization that may elicit an action potential. 

A cell may produce early afterdepolarizations that are depolarization during incomplete repolarization. This is possible if the action potential is considerably prolonged. This is the typical mechanism for elicitation of Torsade de Pointes arrhythmia, a typical complication of class III antiarrhythmics and many other drugs. 

The answer is c. (Katzung, pp 115-117) Overloading of cell Ca leads to delayed afterdepolarizations. These afterpotentials can interfere with normal conduction by further reducing the resting potential if they regularly reach threshold in the conduction system, an arrhythmia can occur. 

Verapamil can suppress both early and delayed afterdepolarizations and may antagonize slow responses arising in severely depolarized tissue. 

Fischbach PS, Corr PB, Yamada KA Long-chain acylcarnitine increases intracellular calcium and induces afterdepolarizations in adult ventricular myocytes (abstracts). Circulation 1992 86(suppl I) 748. 

Zheng, F., Gallagher, J.P. Metabotropic glutamate receptor agonists potentiate a slow afterdepolarization in CNS neurons, Neuroreport. 1992, 3, 622-624. 

Two forms of abnormal activity, early top) and delayed afterdepolarizations bottom). In both cases, abnormal depolarizations arise during or after a normally evoked action potential. They are therefore often referred to as "triggered" automaticity, ie, they require a normal action potential for their initiation. 

Verduyn AC, Vos MA, van der Zande J et at. (1997) Further observations to elucidate the role of interventricular dispersion of repolarization and early afterdepolarizations in the genesis of acquired Torsade de Points arrhythmias. J Am Coll Cardiol 30 1575-1584... 

Vos MA, Verduyn SC, Gorgels APM et al. (1995) Reproducible induction of early afterdepolarizations and torsade de pointes arrhythmias by d-sotalol and pacing in... 

The uncovering of a hidden mechanism of dysrhythmia. For example, antidysrhythmic drugs can cause early or delayed afterdepolarizations, which can result in dysrhythmias. 

Figure 5 Reduction of Irt prolongs action potential duration. Here, the prolongation effects of 25%, 50%, and 75% reduction of h r on APD are shown in a virtual cell model after 1000 paced beats at a cycle length (CL) = 1000 ms. A 75% current reduction results in the development of arrhythmogenic early afterdepolarizations (EADs). [Adapted from (38).]...

Greene C, Schwindt PC, Crill WE 1994 Properties and ionic mechanisms of metabotropic glutamate receptor-mediated slow afterdepolarization in neocortical neurons. J Neurophysiol 72 693-704... 

White G, Lovinger DM, Weight FF 1989 Transient low-threshold Ca current triggers burst firing through an afterdepolarizing potential in an adult mammalian neuron. Proc Natl Acad Sci USA 86 6802-6806... 

Triggered automaticity is also a possible mechanism for abnormal impulse generation. Briefly, triggered automaticity refers to transient membrane depolarizations that occur during repolarization (early after-depolarizations [EADs]) or after repolarization (delayed afterdepolarizations [DADs]) but prior to phase 4 of the action potential. After-depolarizations may be related to abnormal calcium and sodium influx during or just after full cellular repolarization. Experimentally, early after-depolarizations may be precipitated by hypokalemia, type la antiarrhythmic drugs, or slow stimulation rates— any factor that blocks the ion channels (e.g., potassium) responsible... 

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