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The Journal of Neuroscience, December 19, 2007, 27(51):13949-13957; doi:10.1523/JNEUROSCI.3395-07.2007

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Cellular/Molecular
Two Distinct Heterotypic Channels Mediate Gap Junction Coupling between Astrocyte and Oligodendrocyte Connexins

Jennifer L. Orthmann-Murphy,¹ Mona Freidin,² Esther Fischer,² Steven S. Scherer,¹ and Charles K. Abrams²

¹Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6077, and ²Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, New York 11203

Correspondence should be addressed to Jennifer Orthmann-Murphy, University of Pennsylvania Medical Center, Room 464 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA 19104-6077. Email: lorthman{at}mail.med.upenn.edu

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.

Key words: gap junction; glia; myelin; connexin; astrocytes; oligodendrocytes

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Received July 26, 2007; revised Oct. 11, 2007; accepted Oct. 22, 2007.

Correspondence should be addressed to Jennifer Orthmann-Murphy, University of Pennsylvania Medical Center, Room 464 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA 19104-6077. Email: lorthman{at}mail.med.upenn.edu

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