title: Two distinct heterotypic channels mediate gap junction coupling between astrocyte and oligodendrocyte connexins.
abstract: Genetic diseases demonstrate that the normal function of CNS myelin depends on connexin32 (Cx32) and Cx47, gap junction (GJ) proteins expressed by oligodendrocytes. GJs couple oligodendrocytes and astrocytes (O/A channels) as well as astrocytes themselves (A/A channels). Because astrocytes express different connexins (Cx30 and Cx43), O/A channels must be heterotypic, whereas A/A channels may be homotypic or heterotypic. Using electrophysiological and immunocytochemical approaches, we found that Cx47/Cx43 and Cx32/Cx30 efficiently formed functional channels, but other potential heterotypic O/A and A/A pairs did not. These results suggest that Cx30/Cx30 and Cx43/Cx43 channels mediate A/A coupling, and Cx47/Cx43 and Cx32/Cx30 channels mediate O/A coupling. Furthermore, Cx47/Cx43 and Cx32/Cx30 channels have distinct macroscopic and single-channel properties and different dye permeabilities. Finally, Cx47 mutants that cause Pelizaeus-Merzbacher-like disease do not efficiently form functional channels with Cx43, indicating that disrupted Cx47/Cx43 channels cause this disease.
authors: Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6077, USA. lorthman@mail.med.upenn.edu
authors: Jennifer L
authors: JL
authors: Orthmann-Murphy
authors: Mona
authors: M
authors: Freidin
authors: Esther
authors: E
authors: Fischer
authors: Steven S
authors: SS
authors: Scherer
authors: Charles K
authors: CK
authors: Abrams
mesh_terms: D001253:Astrocytes / Q000378:metabolism / Q000502:physiology*; D017630:Connexins / Q000737:chemistry / Q000502:physiology*; D017629:Gap Junctions / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000737:chemistry / Q000502:physiology*; D009836:Oligodendroglia / Q000378:metabolism / Q000502:physiology*
chemical_list: D017630:Connexins; D007473:Ion Channels