title: Atrial fibrillation-linked GJA5/connexin40 mutants impaired gap junctions via different mechanisms.
abstract: The gap junctions (GJs) formed by Cx40 and Cx43 provide a low resistance passage allowing for rapid propagation of action potentials. Sporadic somatic mutations in GJA5 (encoding Cx40) have been identified in lone atrial fibrillation (AF) patients. More recently germline autosomal dominantly inherited mutations in GJA5 have been found in early onset lone AF patients in several families over generations. Characterizations of these AF-linked Cx40 mutants in model cells and in patient tissues revealed that some of the mutants reduced GJ channel function due to an impaired trafficking or channel formation. While others showed a gain-of-function in hemichannels. These functional alterations in GJs or hemichannel may play an important role in the pathogenesis of AF in the mutant carriers.
authors.affiliation: Department of Physiology and Pharmacology, Western University, London, Ontario N6A 5C1, Canada. Electronic address: donglin.bai@schulich.uwo.ca.
authors.forename: Donglin
authors.initials: D
authors.lastname: Bai
mesh_terms: D001281:Atrial Fibrillation / Q000235:genetics / Q000378:metabolism*; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D009154:Mutation; D021381:Protein Transport; D000097003:Gap Junction alpha-5 Protein
chemical_list: D017630:Connexins; D000097003:Gap Junction alpha-5 Protein
keywords: Atrial fibrillation; Autosomal dominant inheritance; Connexin40; Connexin43; Gap junction channel