YIA3Regional Action Potential Gradients in the Murine Left Atrium

BackgroundRegional differences in action potential (AP) morphology in the adult left atrium (LA) may account for susceptibility to atrial fibrillation. The posterior LA wall close to the junction with the pulmonary veins (LA-PV) is an important area contributing to initiation and maintenance of atrial fibrillation. The posterior LA has a distinct embryologic origin: Its development is regulated by PITX2, a gene that has been inflicted in the genetic predisposition to AF. So far, it is not known whether the electrophysiology of the posterior LA differs from that of other parts of the LA. We therefore characterised the electrical phenotype of the LA-PV compared to other LA regions.MethodsTransmembrane (TAPs) and optical (OAPs) action potentials were recorded from 20 superfused murine LA taken from 12 male and 8 female mice aged 12-20 W, bred on an MF1 background. Optical high-density AP mapping was performed and optical APs were recorded from 9 regions across the LA using a dedicated murine activation system (Hamamatsu ORCA flash 4, Di-4-Anepps, sampling rate 1-2 kHz). OAPs were analysed using custom made algorithms produced in MATLAB. At each cycle length, 25 action potentials were averaged to generate a mean waveform that was then used for analysis. TAPs were recorded from 3 LA regions: 1) the posterior LA towards the junction with the pulmonary vein (LA-PV), 2) the medial dome (LA-M) and 3) the LA lateral wall (LA-LW). All Preparations were paced at 100ms.ResultsOAP distribution maps (n = 8 LA) identified a LA-PV to LA-LW pattern of APD shortening and also demonstrated that there is relatively high local APD heterogeneity within the LA-PV region. TAP recordings identified a higher action potential amplitude (APA) in the LA-PV (84 plus or minus 2 mV) than LA-M (78 plus or minus 1 mV, p < 0.05) and LA-LW (77 plus or minus 2 mV, n = 12 LA, p < 0.05). Vmax was greater in the LA-PV (132 plus or minus 10 V/s) than the LA-LW (109 plus or minus 5 V/s, p < 0.05). The resting membrane potential was not different between regions. TAPs were prolonged in the LA-PV compared with the other 2 regions; APD90 LA-PV 28 plus or minus 2 ms, LA-M 21 plus or minus 0.7 ms, LA-LW 19 plus or minus 1 ms, p < 0.05, Figure 1. In addition, APD70 in the LA-LW (11 plus or minus 0.4 ms) was shorter than the LA-M (9 plus or minus 0.4 ms, p < 0.05) suggestive of a more continuous intra-atrial APD gradient. Conduction velocities in different regions will be reported.[Figure]ConclusionRegion