Fig. 6.
Effect of ankyrin-B dysfunction on pacemaking. A: mathematical model of intact sinoatrial node (SAN) based on realistic geometry with cell types determined by immunohistochemistry (3, 13, 42). WT (B) and ankyrin-B+/− (C) activation maps corresponding to one complete cycle (top) and spontaneous APs (bottom) recorded from SAN (black lines) and right atrial free wall (red lines). For ankyrin-B+/−, spontaneous SAN APs are shown for 2 sites (black and gray lines, locations indicated by asterisks) on either side of central block region (white area denoted by arrow). D: simulated and measured (3) conduction velocity from SAN into right atrium (RA). Ankyrin-B dysfunction results in shift of primary pacemaker site toward periphery (central SAN region fails to activate), sinus exit block, and ultimately sinoatrial node failure. E and F: comparison of activation of RA free wall and septum in WT and ankyrin-B+/− for different degrees of fibrosis and different values of cell-to-cell coupling. RA activation properties characterized by number of free wall activations (G), CL of RA activation (H), and latency to first activation (I) in WT, ankyrin-B+/−, Cav1.3-deficient, NKA-deficient, NCX-deficient, and WT with 9% fibrosis. Rg, gap junction resistance.