Figure 5: Functional effects of gain-of-function mutations in SCN5A.

A) Consequences of gain-of-function on the ventricular action potential. Due to an increased net influx of Na⁺-ions, action potential duration is increased (red trace), which can evoke arrhythmic events. B) Different mechanisms that can be responsible for the gain-of-function in I_Na, i.e. increased late current (I_Na,L), increased peak I_Na, decreased rate of inactivation and increased window current. Most commonly, an increase in sustained current (I_Na,L) is observed. C) Shifts in voltage dependence of (in)activation (dashed lines) that lead to an increased window current, as illustrated by the red and blue areas under the curve.