title: The cardiac connexome: Non-canonical functions of connexin43 and their role in cardiac arrhythmias.
abstract: Connexin43 is the major component of gap junctions, an anatomical structure present in the cardiac intercalated disc that provides a low-resistance pathway for direct cell-to-cell passage of electrical charge. Recent studies have shown that in addition to its well-established function as an integral membrane protein that oligomerizes to form gap junctions, Cx43 plays other roles that are independent of channel (or perhaps even hemi-channel) formation. This article discusses non-canonical functions of Cx43. In particular, we focus on the role of Cx43 as a part of a protein interacting network, a connexome, where molecules classically defined as belonging to the mechanical junctions, the gap junctions and the sodium channel complex, multitask and work together to bring about excitability, electrical and mechanical coupling between cardiac cells. Overall, viewing Cx43 as a multi-functional protein, beyond gap junctions, opens a window to better understand the function of the intercalated disc and the pathological consequences that may result from changes in the abundance or localization of Cx43 in the intercalated disc subdomain.
authors.affiliation: The Leon H Charney Division of Cardiology, New York University School of Medicine, New York, NY, United States.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Leo-Macias
authors.affiliation: The Leon H Charney Division of Cardiology, New York University School of Medicine, New York, NY, United States.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Agullo-Pascual
authors.affiliation: The Leon H Charney Division of Cardiology, New York University School of Medicine, New York, NY, United States. Electronic address: mario.delmar@nyumc.org.
authors.forename: Mario
authors.initials: M
authors.lastname: Delmar
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*
chemical_list: D017630:Connexins; D020543:Proteome
keywords: Cx43; Desmosomes; Gap junctions; Intercalated disc; Sodium channels