ArticleCirculation research2020
Cardiomyocyte Expression of ZO-1 Is Essential for Normal Atrioventricular Conduction but Does Not Alter Ventricular Function.
Article in Circulation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Optical mapping: pioneering the frontier of preclinical antiarrhythmic drug evaluation.iScience · 2026Review
- Regulation of Pacemaker Current in the Sinoatrial Node by Zonula Occludens-1.bioRxiv : the preprint server for biology · 2026Article
- CCDC120 phase separation contributes to desmosomal integrity and cardiac function.Nature communications · 2026Article
- Genetic loci responsible for atrioventricular block in children.Frontiers in cell and developmental biology · 2026Review
- Cardiac conduction diseases: understanding the molecular mechanisms to uncover targets for future treatments.Expert opinion on therapeutic targets · 2024Review
- The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.Physiological reviews · 2023Review
- Embryonic Hyperglycemia Disrupts Myocardial Growth, Morphological Development, and Cellular Organization: An In Vivo Experimental Study.Life (Basel, Switzerland) · 2023Article
- The endothelium permeability after bioresorbable scaffolds implantation caused by the heterogeneous expression of tight junction proteins.Materials today. Bio · 2022Article
- Identification of different proteins binding to Na, K-ATPase α1 in LPS-induced ARDS cell model by proteomic analysis.Proteome science · 2022Article
- Article
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
- Zippering Up a Role for ZO-1 in Atrioventricular Node Conduction and Disease.Circulation research · 2020Article
- Mechanotransduction and Adrenergic Stimulation in Arrhythmogenic Cardiomyopathy: An Overview ofFrontiers in physiology · 2020Review
- Mechanism of Left Ventricular Dysfunction due to Permanent Pacemaker: An Analysis of miR-155, sTNFR-2, MMP-9, N-Cad, and ZO-1.Journal of cardiovascular echographyArticle
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleZO-1 (Zonula occludens-1), a plasma membrane-associated scaffolding protein regulates signal transduction, transcription, and cellular communication. Global deletion of ZO-1 in the mouse is lethal by embryonic day 11.5. The function of ZO-1 in cardiac myocytes (CM) is largely unknown.
objectiveTo determine the function of CM ZO-1 in the intact heart, given its binding to other CM proteins that have been shown instrumental in normal cardiac conduction and function. METHODS AND
resultsWe generated ZO-1 CM-specific knockout (KO) mice using α-Myosin Heavy Chain-nuclear Cre (ZO-1cKO) and investigated physiological and electrophysiological function by echocardiography, surface ECG and conscious telemetry, intracardiac electrograms and pacing, and optical mapping studies. ZO-1cKO mice were viable, had normal Mendelian ratios, and had a normal lifespan. Ventricular morphometry and function were not significantly different between the ZO-1cKO versus control (CTL) mice, basally in young or aged mice, or even when hearts were subjected to hemodynamic loading. Atrial mass was increased in ZO-1cKO. Electrophysiological and optical mapping studies indicated high-grade atrioventricular (A-V) block in ZO-1cKO comparing to CTL hearts. While ZO-1-associated proteins such as vinculin, connexin 43, N-cadherin, and α-catenin showed no significant change with the loss of ZO-1, Connexin-45 and Coxsackie-adenovirus (CAR) proteins were reduced in atria of ZO-1cKO. Further, with loss of ZO-1, ZO-2 protein was increased significantly in ventricular CM in a presumed compensatory manner but was still not detected in the AV nodal myocytes. Importantly, the expression of the sodium channel protein NaV1.5 was altered in AV nodal cells of the ZO-1cKO versus CTL.
conclusionsZO-1 protein has a unique physiological role in cardiac nodal tissue. This is in alignment with its known interaction with CAR and Cx45, and a new function in regulating the expression of NaV1.5 in AV node. Uniquely, ZO-1 is dispensable for function of the working myocardium.
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