The inactivation of the L-type Ca 2+ current is composed of voltage-dependent and calcium-dependent mechanisms. The relative contribution of these processes is still under dispute and the idea that the voltage-dependent inactivation could be subject to further modulation by other physiological processes had been ignored. This study sought to model physiological modulation of inactivation of the current in cardiac ventricular myocytes, based upon the recent detailed experimental data that separated total and voltage-dependent inactivation (VDI) by replacing extracellular Ca 2+ with Mg 2+ and monitoring L-type Ca 2+ channel behaviour by outward K + current flowing through the channel in the absence of inward current flow. Calcium-dependent inactivation (CDI) was based upon Ca 2+ influx and formulated from data that was recorded during β-adrenergic stimulation of the myocytes. Ca 2+ influx and its competition with non-selective monovalent cation permeation were also incorporated into channel permeation in the model. The constructed model could closely reproduce the experimental Ba 2+ and Ca 2+ current results under basal condition where no β-stimulation was added after a slight reduction of the development of fast voltage-dependent inactivation with depolarization. The model also predicted that under β-adrenergic stimulation voltage-dependent inactivation is lost and calcium-dependent inactivation largely compensates it. The developed model thus will be useful to estimate the respective roles of VDI and CDI of L-type Ca 2+ channels in various physiological and pathological conditions of the heart which would otherwise be difficult to show experimentally.