INa model parameters are optimized to match simulation outputs (lines) with experiments (symbols, from [15, 19, 22, 23]). A–C) Peak INa-Em relationship (normalized to maximal peak current in drug-free condition), activation, and steady-state inactivation with or without 10 µM ranolazine. D) Dose-dependence of tonic block for peak and late INa evoked by a 200-ms depolarizing pulse from −100 to −10 mV. Current amplitude in the presence of ranolazine is normalized to the current amplitude in the absence of drug. E–F) Dose- and frequency-dependence of UDB from a train of 300 25-ms long pulses (from −100 to −10 mV). INa amplitude in the presence of ranolazine at the last pulse is normalized to INa amplitude in drug-free condition.