Fig. 6

Model simulation, assuming an inhomogeneous distribution of intrinsic properties of SAN cells, reproduced dissociation between the leading pacemaker site and the region of maximum phase-4 slope. A two-dimensional sheet model consisting of 25 × 25 Kyoto-model SAN cells was evaluated. Random distributions of L-type Ca²⁺ current amplitudes were assumed to simulate the inhomogeneous structure of the SAN. Upper and lower panels represent the activation patterns with gap junction conductances of 20 and 10 nS/cell, respectively. The asterisk indicates the location of the cell that has the shortest cycle length. a The dissociation between the leading pacemaker site and the cell (site) with the maximum linearly rising early phase-4 with the gap junction conductance of 20 nS/cell is explained by a steeper exponentially rising late phase-4 slope at the leading pacemaker site shown in the inset. The left panel indicates entire action potential waveforms and the right panel shows expanded action potential waveforms. The red trace illusrates the action potential trajectory of the leading pacemaker site (open circle on activation map); the blue trace presents the action potential trajectory of the cell with the maximum phase-4 slope (open triangle on phase-4 slope map). The reduction in the gap junction conductance changed the spatial distribution of action potential characteristics and shifted the leading pacemaker site. The leading pacemaker site shifted from the lower center to the bottom left corner where the phase-4 slope was the maximum. b The reduction in the gap junction conductance caused bifocal activation in the left region. These new leading pacemaker sites coincided with regions of locally maximum phase-4 slope