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Connexin Hemichannels in Astrocytes: An Assessment of Controversies Regarding Their Functional Characteristics

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Abstract

Astrocytes in the mammalian central nervous system are interconnected by gap junctions made from connexins of the subtypes Cx30 and Cx43. These proteins may exist as hemichannels in the plasma membrane in the absence of a ‘docked’ counterpart on the neighboring cell. A variety of stimuli are reported to open the hemichannels and thereby create a permeation pathway through the plasma membrane. Cx30 and Cx43 have, in their hemichannel configuration, been proposed to act as ion channels and membrane pathways for different molecules, such as fluorescent dyes, ATP, prostaglandins, and glutamate. Published studies about astrocyte hemichannel behavior, however, have been highly variable and/or contradictory. The field of connexin hemichannel research has been complicated by great variability in the experimental preparations employed, a lack of highly specific pharmacological inhibitors and by confounding changes associated with genetically modified animal models. This review attempts to critically assess the gating, inhibition and permeability of astrocytic connexin hemichannels and proposes that connexins in their hemichannel configuration act as gated pores with isoform-specific permeant selectivity. We expect that some, or all, of the controversies discussed here will be resolved by future research and sincerely hope that this review serves to motivate such clarifying investigations.

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Funding

This study was supported by Sundhed og Sygdom, Det Frie Forskningsråd (Grant No. 10-081105).

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Authors and Affiliations

  1. Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, Bldg. 22.3, 2200, Copenhagen, Denmark

    Brian Skriver Nielsen & Nanna MacAulay

  2. Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK

    Daniel Bloch Hansen

  3. Department of Neurology, University of Washington, Seattle, USA

    Bruce R. Ransom

  4. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Morten Schak Nielsen

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  1. Brian Skriver Nielsen
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  2. Daniel Bloch Hansen
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Correspondence to Nanna MacAulay.

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Nielsen, B.S., Hansen, D.B., Ransom, B.R. et al. Connexin Hemichannels in Astrocytes: An Assessment of Controversies Regarding Their Functional Characteristics. Neurochem Res 42, 2537–2550 (2017). https://doi.org/10.1007/s11064-017-2243-7

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