Connexin40 knockout mice demonstrated slower right atrial conduction compared to wild-type mice (0.61 vs 0.94 m/s; P<0.05), along with intra-atrial block and ectopic rhythms.
Does Connexin40 knockout alter intra-atrial excitation and propagation in mice?
Connexin40 knockout in mice leads to intra-atrial block, ectopic rhythms, and altered atrial propagation, highlighting its role in atrial impulse propagation.
Absolute Event Rate: 0.61% vs 0.94%
p-value: p=<0.05
BACKGROUND: Intercellular coupling via connexin40 (Cx40) gap junction channels is an important determinant of impulse propagation in the atria. METHODS AND RESULTS: We studied the role of Cx40 in intra-atrial excitation and propagation in wild-type (Cx40(+/+)) and knockout (Cx40(-/-)) mice using high-resolution, dual-wavelength optical mapping. On ECG, the P wave was significantly prolonged in Cx40(-/-) mice (13.4+/-0.5 versus 11.4+/-0.3 ms in Cx40(+/+)). In Cx40(+/+) hearts, spontaneous right atrial (RA) activation showed a focal breakthrough at the junction of the right superior vena cava, sulcus terminalis, and RA free wall, corresponding to the location of the sinoatrial node. In contrast, Cx40(-/-) hearts displayed ectopic breakthrough sites at the base of the sulcus terminalis, RA free wall, and right superior vena cava. Progressive ablation of such sites in 4 Cx40(-/-) mice resulted in ectopic focus migration and cycle length prolongation. In all Cx40(-/-) hearts the focus ultimately shifted to the sinoatrial node at a very prolonged cycle length (initial ectopic cycle length, 182+/-20 ms; postablation sinus cycle length, 387+/-44 ms). In a second group of experiments, epicardial pacing at 10 Hz revealed slower conduction in the RA free wall of 5 Cx40(-/-) hearts than in 5 Cx40(+/+) hearts (0.61+/-0.07 versus 0.94+/-0.07 m/s; P<0.05). Dominant frequency analysis in Cx40(-/-) RA demonstrated significant reduction in the area of 1:1 conduction at 16 Hz (40+/-10% versus 69+/-5% in Cx40(+/+)) and 25 Hz (36+/-11% versus 65+/-9% in Cx40(+/+)). CONCLUSIONS: This is the first demonstration of intra-atrial block, ectopic rhythms, and altered atrial propagation in the RA of Cx40(-/-) mice.
Bagwe et al. (Tue,) conducted a other in Altered Right Atrial Excitation and Propagation. Connexin40 knockout vs. Wild-type (Cx40(+/+)) mice was evaluated on Conduction velocity in the right atrial free wall during epicardial pacing at 10 Hz (p=<0.05). Connexin40 knockout mice demonstrated slower right atrial conduction compared to wild-type mice (0.61 vs 0.94 m/s; P<0.05), along with intra-atrial block and ectopic rhythms.