title: Gap junctions.
abstract: Gap junctions are essential to the function of multicellular animals, which require a high degree of coordination between cells. In vertebrates, gap junctions comprise connexins and currently 21 connexins are known in humans. The functions of gap junctions are highly diverse and include exchange of metabolites and electrical signals between cells, as well as functions, which are apparently unrelated to intercellular communication. Given the diversity of gap junction physiology, regulation of gap junction activity is complex. The structure of the various connexins is known to some extent; and structural rearrangements and intramolecular interactions are important for regulation of channel function. Intercellular coupling is further regulated by the number and activity of channels present in gap junctional plaques. The number of connexins in cell-cell channels is regulated by controlling transcription, translation, trafficking, and degradation; and all of these processes are under strict control. Once in the membrane, channel activity is determined by the conductive properties of the connexin involved, which can be regulated by voltage and chemical gating, as well as a large number of posttranslational modifications. The aim of the present article is to review our current knowledge on the structure, regulation, function, and pharmacology of gap junctions. This will be supported by examples of how different connexins and their regulation act in concert to achieve appropriate physiological control, and how disturbances of connexin function can lead to disease.
authors.affiliation: Department of Biomedical Sciences and The Danish National Research Foundation Centre for Cardiac Arrhythmia, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten Schak
authors.initials: MS
authors.lastname: Nielsen
authors.forename: Lene Nygaard
authors.initials: LN
authors.lastname: Axelsen
authors.forename: Paul L
authors.initials: PL
authors.lastname: Sorgen
authors.forename: Vandana
authors.initials: V
authors.lastname: Verma
authors.forename: Mario
authors.initials: M
authors.lastname: Delmar
authors.forename: Niels-Henrik
authors.initials: NH
authors.lastname: Holstein-Rathlou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002450:Cell Communication; D017630:Connexins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport
chemical_list: D017630:Connexins