Cardiomyocyte Loss of Mouse Zo-1 Causes Abnormal Conduction but is Dispensable for Contractile Function

Introduction: Zonula occludens-1 (ZO-1) is a scaffolding protein that regulates signal transduction, transcription, and cellular communication in many cell types. Global ZO-1 knockout mice die at embryonic 11.5 day, yet the function of ZO-1 in cardiomyocytes (CMs) is largely unknown. Hypothesis: ZO-1 protein plays a critical role in cardiac function. Methods: ZO-1 floxed mice were constructed and crossed with α-Myosin Heavy Chain-Cre mice (ZO-1cKO). Physiological, electrophysiological (EP) and biochemical evaluations were performed. Results: Hearts of ZO-1cKO mice up to 20m age showed no histological, morphometric or functional changes vs. heterozygous ZO-1cKO (controls) other than increased atrial mass. Surface ECG and telemetry displayed supraventricular arrhythmias in ZO-1cKO mice (fig). EP studies showed various atrioventricular (AV) blocks in ZO1cKO, including high-grade 2nd-degree and complete AV block, at 4m. The P-P interval was increased in ZO-1cKO in sinus rhythm vs. controls (0.177±0.018 vs. 0....