Figure 5.
Effect of a specific reduction of If on AP firing rate is mediated via perturbation of both M-clock and Ca2+ clock. Simulations using the Maltsev-Lakatta model (10) with integrated mitochondrial Ca2+ dynamics predict the effects of IVA on (A) If, (B) AP, (C) ICaL, (D) cytosolic Ca2+, (E) junctional, (F) network SR [Ca2+], and (G) sarolemmal INCX. “Control”: model simulations prior to drug. “Change only in If”: model simulations when only If conductance is reduced. “Change in If and SERCA”: model simulations when both If and SR Ca2+ pumping (SERCA) parameters were changed. The dashed lines represent the respective diastolic DD phases. From (71).