Fig. 1.

The ventricular action potential. Ventricular action potential simulated in python NEURON [150] using an adaptation of the DiFrancesco and Noble model [151] and stimulating with a 2 nA current injection at time 0.2 s. The four phases of the action potential are illustrated on the waveform. Phase 0 is the upstroke of the action potential resulting from the large rapid sodium (Na⁺) current, activated once the activation threshold is exceeded. Phase 1 occurs from the inactivation of the Na⁺ current while there is activation of a transient outward potassium (K⁺) current. Phase 2 is the plateau largely resulting from a balanced inward calcium (Ca²⁺) and outward delayed rectifier (K⁺) current. Phase 3, the downward stroke, occurs as the Ca²⁺ inactivates whilst the delayed rectifier current persists. In a ventricular myocyte, by phase 4 the cell has returned to the resting membrane potential and the voltage-gated currents will “reset” (recover from inactivation), ready for the next action potential. A key difference in nodal tissues (e.g. sinoatrial node) is that phase 4 of the nodal action potential (not shown) is a period of spontaneous depolarisation. Some established anti-arrhythmic drugs modulate specific phases of the action potential by their effects on specific ion currents e.g. Na⁺ (quinidine, lidocaine, mexiletine, flecainide) and K⁺ (amiodarone, sotalol, dofetilide). For instance, amiodarone modulates the hERG (human Ether-à-go-go-Related Gene) K⁺ channel that controls action potential duration [152].