PMID- 18094232 OWN - NLM STAT- MEDLINE DCOM- 20080114 LR - 20240419 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 27 IP - 51 DP - 2007 Dec 19 TI - Two distinct heterotypic channels mediate gap junction coupling between astrocyte and oligodendrocyte connexins. PG - 13949-57 AB - 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. FAU - Orthmann-Murphy, Jennifer L AU - Orthmann-Murphy JL AD - Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6077, USA. lorthman@mail.med.upenn.edu FAU - Freidin, Mona AU - Freidin M FAU - Fischer, Esther AU - Fischer E FAU - Scherer, Steven S AU - Scherer SS FAU - Abrams, Charles K AU - Abrams CK LA - eng GR - R01 NS050705-03/NS/NINDS NIH HHS/United States GR - R01 NS055284/NS/NINDS NIH HHS/United States GR - K02 NS050345-03/NS/NINDS NIH HHS/United States GR - NS054363/NS/NINDS NIH HHS/United States GR - NS043560/NS/NINDS NIH HHS/United States GR - NS50345/NS/NINDS NIH HHS/United States GR - K02 NS050345-02/NS/NINDS NIH HHS/United States GR - NS55284/NS/NINDS NIH HHS/United States GR - R01 NS050705-02/NS/NINDS NIH HHS/United States GR - F30 NS054363/NS/NINDS NIH HHS/United States GR - R01 NS050705/NS/NINDS NIH HHS/United States GR - K02 NS050345/NS/NINDS NIH HHS/United States GR - R01 NS043560/NS/NINDS NIH HHS/United States GR - NS050705/NS/NINDS NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Connexins) RN - 0 (Ion Channels) SB - IM MH - Astrocytes/metabolism/*physiology MH - Connexins/chemistry/*physiology MH - Gap Junctions/chemistry/*metabolism/physiology MH - HeLa Cells MH - Humans MH - Ion Channel Gating/physiology MH - Ion Channels/chemistry/*physiology MH - Oligodendroglia/metabolism/*physiology PMC - PMC6673504 EDAT- 2007/12/21 09:00 MHDA- 2008/01/15 09:00 PMCR- 2008/06/19 CRDT- 2007/12/21 09:00 PHST- 2007/12/21 09:00 [pubmed] PHST- 2008/01/15 09:00 [medline] PHST- 2007/12/21 09:00 [entrez] PHST- 2008/06/19 00:00 [pmc-release] AID - 27/51/13949 [pii] AID - 3294191 [pii] AID - 10.1523/JNEUROSCI.3395-07.2007 [doi] PST - ppublish SO - J Neurosci. 2007 Dec 19;27(51):13949-57. doi: 10.1523/JNEUROSCI.3395-07.2007.