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. Author manuscript; available in PMC: 2020 Aug 1.
Published in final edited form as: J Physiol. 2019 Jul 11;597(15):3867–3883. doi: 10.1113/JP278016

Figure 8.

Figure 8.

AP-clamp (A-H) and current clamp (I-J) simulations with species-specific electrophysiological models. (A-D) AP-clamp simulation was performed with a train of rabbit or mouse APs mimicking in rate and duration the experimental responses to sympathetic nerve stimulation (black lines with symbols), a train of constant APDs with increased rate (blue lines), or a train of APDs in which the species-specific responses (APD fractional changes) were swapped (grey lines). In all simulations, rate was increased according to experimental responses (red lines with symbols) and ISO (100 nM) was applied at time 0. (E) In rabbit, APD shortening increased steady-state enhancement in CaT amplitude compared to both constant APD and transiently prolonged APD (black versus blue and grey lines). (F) In mouse, transient APD prolongation enhanced the early CaT increase compared to constant APD (peak at approx. 20 sec, black versus blue line) and transient prolongation produced substantial increase in CaT compared to a monotonic decrease in APD (black versus grey line). (G) In rabbit, APD shortening hastened early and steady-state CaT decay (CaT τdecay) compared to the simulation in which APD was held constant (black versus blue line), and hastened early CaT decay compared to transient APD prolongation (black versus grey line). (H) In mouse, APD prolongation hastened early CaT τdecay compared to constant APD (at approx. 30 sec, black versus blue line). Steady-state responses were comparable (as the APD is back to its initial value). Monotonic APD shortening produced slower early and steady-state CaT decay. (I) Current-clamp simulation of SNS-like conditions produced a monotonic decrease in rabbit APD, which was in good agreement with experimental data. (J) Current-clamp simulation in mouse produced a slight increase in APD (blue line), but did not fully replicate the biphasic response observed experimentally. When the effect of PKA on IKur was changed to a 100% increase (from a 20% increase) with a slower phosphorylation time constant (30s vs 10s), a biphasic APD response was elicited (green line).