Skip to main content
. 2022 Oct 18;11:e77327. doi: 10.7554/eLife.77327

Figure 5. SAN dysfunction in the Dnajb6+/- mice.

(A) Leading pacemakers were located and plotted from both WT (blue dots) and Dnajb6+/- (red dots) mice. One mouse could have multiple leading pacemaker locations due to the competing pacemakers and ectopic activities. SVC and IVC, superior and inferior vena cava; RAA, right atrial appendage; CT, crista terminalis; IAS, inter-atrial septum; AVN, atrioventricular node. Distribution of the leading pacemakers is summarized in panel. (B) Majority of leading pacemakers located within the SAN area in WT, whereas, in Dnajb6+/- mice, significant increase of leading pacemakers locating in subsidiary pacemaker area and IAS was observed. p-value by Fisher exact test. (C–D) Activation map based on the optical mapping of action potentials showed representative leading pacemaker locations in WT (SAN) and Dnajb6+/- mice (SAN and IAS areas). (E) Optical mapping on isolated atrial preparation showed bradycardia (baseline) and different responses of heart rate during isoproterenol, atropine, and carbachol stimulations between WT and Dnajb6+/- mice. N=7–9 mice per group. Unpaired student’s t-test. (F) Increased cycle length (CL) variation was observed in Dnajb6+/- isolated atrial preparations during different autonomic stimulations. N = 7–9 mice per group, unpaired student’s t-test.

Figure 5.

Figure 5—figure supplement 1. Sinus node recovery time was prolonged in the Dnajb6+/- mice.

Figure 5—figure supplement 1.

(A–B) Representative activation maps reconstructed for the last pacing stimulus (S1) and the first spontaneous post-pacing atrial beat (A1) during SAN recovery time (SANRT) measurements are shown. A site of the earliest atrial activation is labeled by a white asterisk. In Dnajb6+/- group, unlike WT, the first spontaneous post-pacing atrial beat (A1) originated from an ectopic location outside of the anatomically and functionally defined SAN area. (C) Summarized data for corrected SANRT (+/-) measured during different autonomic stimulations is shown. N=7–9 mice per group, unpaired student’s t-test.
Figure 5—figure supplement 2. Fibrotic tissue content in atrial and SAN myocardium of Dnajb6+/-vs.WT mice.

Figure 5—figure supplement 2.

(A–B) Masson’s Trichrome (A) and Picrosirius Red (B) staining of WT and Dnajb6+/- mice are shown for left (LAA) and right (RAA) atrial appendages as well as SAN regions. Below the representative images, summarized data for fibrotic to myocardial tissue ratio are shown for each staining. N=4 mice per group. Scale bars, 100 µm.