Effects of the E161K mutation in SCN5A, either in H558 or R558 background, on the spontaneous activity of the Fabbri-Severi model of a human SA nodal pacemaker cell. (A) Membrane potential (Vm), and associated (B) intracellular calcium concentration ([Ca2+]i), (C) net membrane current (Inet), (D) L-type calcium current (ICaL) and total repolarizing current (Irepol), (E) T-type calcium current (ICaT) and sodium-calcium exchange current (INCX), (F) ACh-activated potassium current (IK,ACh) and hyperpolarization-activated “funny current” (If), and (G) fast sodium current (INa) in the absence of ACh. (H) Vm, (I) [Ca2+]i, (J) Inet, (K) ICaL and Irepol, (L) ICaT and INCX, (M) IK,ACh, and If, and (N) INa during simulated administration of 10 nM ACh. Solid gray lines show the effect of a 50% reduction in fully-activated conductance of INa (gNa). Horizontal arrows indicate increase in cycle length. Irepol consists of IK,ACh, the rapid delayed rectifier potassium current IKr, the slow delayed rectifier potassium current IKs, the ultrarapid delayed rectifier potassium current IKur, the transient outward potassium current Ito, and the sodium-potassium pump current INaK.