Figure 1.
A) the action potential of an isolated cell in response to a short current pulse injection (4 nA, 5 ms); B) schematic representation of the gap junctions connecting neighbor cells, represented by arrows; C) the gap junction conductance as a function of the junctional potential under control conditions (black line) and for cells forming the edges of the fibrotic area (red line); D) Schematic representation of the full 128×256 cell network; individual cells are represented with small purple (normal) or yellow (ischemic) rectangles; the black lines identify the contour of the lesion, composed by non-conducting cells (i.e. g = 0). Cells with rectifying gap junctions, implementing entry and exit doors are shown in gray. Physiological input signals from Purkinje cells were modeled by periodically stimulating with a short current pulse cell(1,1) (bottom left of the network, shown in red); E) typical membrane potential of cell(25,100) under physiological conditions (i.e. no ischemic area).
Figure 2.
Typical experimental ECG recordings showing the different arrhythmias taken into account by our model.
A) single premature ventricular beat; B) trigeminy complexes; C) bigeminy complexes; D) couplet episode; E) triplet episode; F) two short runs of tachyarrhythmias. In all cases, markers highlight arrhythmic complexes.
Figure 3.
Typical onset of a premature beat.
A–I) snapshots from Movie S2, illustrating the propagation of two normal beats (panels A-B-C and I) and a premature beat (panels D through H); (bottom plot): membrane potential of cell(25,100), marked in yellow in the snapshots, during the simulation shown in Movie S2. Vertical markers show the time points at which the snapshots in panels A-I were taken.
Figure 4.
Our model suggests that all kinds of arrhythmia can be explained by dynamical fluctuations of the gap junctions.
A) (top to bottom) isolated arrhythmia, trigeminy complex, bigeminy complex, couplet, triplet, short runs of tachyarrhythmias followed by a bigeminism; compare all panels with those in Fig. 2; B) 25 sec simulation exhibiting different types of arrhythmic behavior. In all cases, red markers highlight abnormal sequences (see Table 1); traces represent the membrane potential of cell(25,100), from simulations with the following average gap junction conductance and variance: (4.7, 0.3) iPVB, (4.9, 0.3) trigeminy, bigeminy, and triplet, (4.7, 0.6) couplet, (4.7, 0.8) VT.
Table 1.
Specific sequences of interspike interval (ISI) define normal or abnormal behavior; X normal ISI; −, shorter than normal; +, longer than normal.
Figure 5.
Gap junction modulations and fluctuations inside an ischemic area determine the relative proportion of premature beats.
A) Percent of premature beats, with respect to the total number of beats, generated by different average and variance values of the gap junction conductance inside the ischemic area; B) Distribution of abnormal events as a function of the variance (top graph) or the average value (bottom graph) of the gap junctions conductance inside the ischemic area. White bars represent iPVB.
Figure 6.
The generation of premature beats may depend on the direction of signal propagation.
A) schematic representation of the two ischemic areas investigated, and the two stimulation points (O1 and O2) used to model different directions for the propagation of a physiological signal; B) Proportion of premature beats as function of the variance of the gap junction conductance inside the ischemic area for different stimulation points. The average value of the gap junction conductance of the cells inside the ischemic area was 4.7 nS in all cases.