•  Abnormal oscillations of calcium (Ca2+) concentration in cardiac Purkinje cells (P‐cells) have been associated with life‐threatening arrhythmias, but the mechanism by which these cells control their Ca2+ level in normal conditions remains unknown. •  We modelled our previous hypothesis that the principal intracellular Ca2+ compartment (endoplasmic reticulum; ER) which governs intracellular Ca2+ concentration, formed, in P‐cells, three concentric and adjacent layers, each including a distinct Ca2+ release channel. We then tested the model against typical Ca2+ variations observed in stimulated P‐cells. •  We found in swine P‐cells, as in the rabbit and dog, that stimulation evokes an elevation of Ca2+ concentration first under the membrane, which then propagates to the interior of the cell. •  Our mathematical model could reproduce accurately this typical ‘centripetal’ Ca2+ spread, hence supporting (1) the existence of the ‘3 layered’ Ca2+ compartment, and (2) its central role in the regulation of Ca2+ concentration in P‐cells. •  To model the ‘centripetal’ Ca2+ spread, local variations of Ca2+ concentration were calculated for a virtual cell environment encompassing three different regions that mimicked the three layers of ER in P‐cells. Various tests of the model revealed that the second intermediate layer was essential for ‘forwarding’ the Ca2+ elevation from the periphery to the cell centre. •  This novel finding suggests that a thin intermediate layer of specific ER Ca2+ channels controls the entire Ca2+ signalling of P‐cells. Because Ca2+ plays a role in the electric properties of P‐cells, any abnormality affecting this intermediate region is likely to be pro‐arrhythmic and could explain the origin of serious cardiac arrhythmias known to start in the Purkinje fibres. Abstract  Despite strong suspicion that abnormal Ca2+ handling in Purkinje cells (P‐cells) is implicated in life‐threatening forms of ventricular tachycardias, the mechanism underlying the Ca2+ cycling of these cells under normal conditions is still unclear. There is mounting evidence that P‐cells have a unique Ca2+ handling system. Notably complex spontaneous Ca2+ activity was previously recorded in canine P‐cells and was explained by a mechanistic hypothesis involving a triple layered system of Ca2+ release channels. Here we examined the validity of this hypothesis for the electrically evoked Ca2+ transient which was shown, in the dog and rabbit, to occur progressively from the periphery to the interior of the cell. To do so, the hypothesis was incorporated in a model of intracellular Ca2+ dynamics which was then used to reproduce numerically the Ca2+ activity of P‐cells under stimulated conditions. The modelling was thus performed through a 2D computational array that encompassed three distinct Ca2+ release nodes arranged, respectively, into three consecutive adjacent regions. A system of partial differential equations (PDEs) expressed numerically the principal cellular functions that modulate the local cytosolic Ca2+ concentration (Cai). The apparent node‐to‐node progression of elevated Cai was obtained by combining Ca2+ diffusion and ‘Ca2+‐induced Ca2+ release’. To provide the modelling with a reliable experimental reference, we first re‐examined the Ca2+ mobilization in swine stimulated P‐cells by 2D confocal microscopy. As reported earlier for the dog and rabbit, a centripetal Ca2+ transient was readily visible in 22 stimulated P‐cells from six adult Yucatan swine hearts (pacing rate: 0.1 Hz; pulse duration: 25 ms, pulse amplitude: 10% above threshold; 1 mm Ca2+; 35°C; pH 7.3). An accurate replication of the observed centripetal Ca2+ propagation was generated by the model for four representative cell examples and confirmed by statistical comparisons of simulations against cell data. Selective inactivation of Ca2+ release regions of the computational array showed that an intermediate layer of Ca2+ release nodes with an ∼30–40% lower Ca2+ activation threshold was required to reproduce the phenomenon. Our computational analysis was therefore fully consistent with the activation of a triple layered system of Ca2+ release channels as a mechanism of centripetal Ca2+ signalling in P‐cells. Moreover, the model clearly indicated that the intermediate Ca2+ release layer with increased sensitivity for Ca2+ plays an important role in the specific intracellular Ca2+ mobilization of Purkinje fibres and could therefore be a relevant determinant of cardiac conduction.