Fig. 4.

Simulated effects of α₂δ-1 depletion on cardiac APs and Ca²⁺ transients. (A) Experimentally determined effects of α₂δ-1 depletion on cardiac L-type Ca²⁺ currents (compare Figs. 2 and 3) were simulated by introducing the relative changes of τ_activation, τ_inactivation, voltage-dependence, and amplitude into a dynamic computer model of ventricular myocytes (see also SI Methods). (B) The simulated I–V curves show the contribution of each parameter affected by α₂δ-1 depletion to the observed reduction of the current amplitude. Whereas the voltage shift contributed strongly to the reduced current amplitude, kinetic changes showed little effects. (C–E) Simulating the consequences of α₂δ-1 depletion on cardiac APs, Ca²⁺ currents and cytoplasmic Ca²⁺ concentration during the AP (red trace) predicts a decreased rate of repolarization during the plateau phase and a 60%-increased duration of the AP measured at AP/2. Peak [Ca²⁺] is predicted to increase by 123%.