Figure 1.

Schematic of cardiac APs studied using dynamic clamp to test properties of virtual I_Ca,L to eliminate EADs by Madhvani et al. (2015). A normal ventricular AP (left) with the major phases of AP repolarization indicated (2 and 3). The AP is prolonged in response to oxidative stress (H₂O₂) or hypokalemia (Low[K⁺]_o), leading to an EAD (bottom). Complete block of I_Ca,L with a calcium channel blocker, nifedipine, dramatically shortens the AP and eliminates EAD (right). Using a computer model to generate virtual I_Ca,L, a dynamic clamp reconstitutes the missing I_Ca,L and recapitulates the long AP and EAD (top). By systematically changing the gating properties of virtual I_Ca,L, Madhvani et al. (2015) test for properties of the current that will preserve peak current and contraction but eliminate EADs.