Figure 4.

Computer modeling of action potentials (APs) of cells expressing only wild-type Na⁺ channels (solid line), a 1:1 (i.e., heterozygous) mixture of mutant (MT) and wild-type (WT) channels (dashed line), or a mixture of MT and WT channels after simulated rescue with mexiletine (bold line). The decreased inward current from MT channels reduced the AP upstroke velocity from 371 V/s to 232 V/s and the sustained inward current slightly prolonged AP duration. Upon simulated rescue of all MT channels (normal I_Na amplitude) and without continued drug present, the AP was significantly prolonged and an early afterdepolarization was generated.