Action potential duration restitution portraits of mammalian ventricular myocytes: Role of calcium current

Construction of the action potential duration (APD) restitution portrait allows visualization of multiple aspects of the dynamics of periodically paced myocytes at various basic cycle lengths (BCLs). For the first time, we obtained the restitution portrait of isolated rabbit and guinea pig cardiac ventricular myocytes and analyzed the time constant, τ, of APD accommodation and the slopes of different types of restitution curves, S_dyn and S ₁₂, measured at varying BCLs. Our results indicate that both τ and the individual slopes are species and pacing dependent. In contrast, the mutual relationship between slopes S_dyn and S₁₂ does not depend on pacing history, being a generic feature of the species. In addition, the maximum slope S₁₂, measured in the restitution portrait at the lowest BCL, predicts the onset of alternans. Further, we investigated the role of the L-type calcium current, I_Ca-L, in the restitution portrait. We found that I_Ca-L dramatically affects APD accommodation, as well as the individual slopes S_dyn and S₁₂ measured in the restitution portrait. However, peak calcium current plays a role only at small values of BCL. In conclusion, the results demonstrate that the restitution portrait is a powerful technique to investigate restitution properties of periodically paced cardiac myocytes and the onset of alternans, in particular. Moreover, the data also show that I_Ca-L plays a crucial role in multiple aspects of cardiac dynamics measured through the restitution portrait.