To evaluate AF susceptibility, we carried out a transvenous burst pacing to induce atrial fibrillation. After programmed stimulation, compared to the WT + AAV-CON (1/10) and WT + AAV-Chrna7 (1/10) groups, a higher AF incidence were observed in the mice of APP/ PS1+AAV-CON (7/10) group. which were attenuated by AAV-Chrna7 (3/10) (Fig. 7A and B). The AF duration of APP/PS1+ AAV-CON mice was significantly higher compared with the other three groups (Fig. 7C). These data indicated that APP/PS1 mice increased the AF susceptibility and persistency, which could be suppressed by silencing α7nAChR. Furthermore, in order to investigate the atrial electrical remodeling, we performed a protocol of the cardiac perfusion using nicotine, an α7nAChR agonist, or α-BTX, an α7nAChR antagonist. Electrophysiological mapping experiment showed that the atrial conduction velocity was markedly decreased by nicotine perfusion in the Langendorffisolated hearts of WT. Surprisingly, nicotine did not significantly reduce the atrial conductivity of APP/PS1 mice, which might be due to the fact that both nicotine and Aβ act on α7nAChR, leading to a saturation effect. However, α-BTX resulted in increased atrial conductivity in both mice (Fig. 7D–F). As shown in Fig. 7E, ectopic pacing (black arrow) was shown in APP/PS1 group. The nicotine-induced upregulation of calculated dispersion was restrained by α-BTX in APP/PS1 isolated hearts, but not in WT group (Fig. 7G). These results indicate that inhibition of α7nAChR ameliorate

Silencing α7nAChR blocked the high AF susceptibility and atrial electrical anomalies of APP/PS1 mice. (A) Representative electrocardiogram AF episodes induced by intra-atrial burst pacing. (B) Quantitative analysis of AF incidence (n = 10). (C) Quantitative analysis of AF duration (n = 10). (D) Schematic of the experimental design of epicardial electrical mapping recording. (E) Successive isochronal conduction maps of left atria of WT and APP/PS1 mice. Black arrow means ectopic pacing. (F) Quantitative analysis of atrial conduction velocity (n = 6). (G) Quantitative analysis of Inhomogeneity index (n = 6). Data were presented as Mean ± S.D. ns P > 0.05, *P < 0.05, **P < 0.01 and ***P < 0.001.

https://doi.org/10.1016/j.redox.2022.102594